Histology_Ross

Histology_Ross. This view of the endometrium in the secretory phase shows the stratum functionale (SF), the stratum basale (SB), and, in the lower left of the photomicrograph, a small amount of the myometrium (M). The uterine glands have been cut in a plane that is close to their long axes, and one gland (arrow) is seen opening at the uterine surface. Except for a few glands near the center of the figure that resemble those of the proliferative phase, most of the glands (Gl) in this figure, including those that are labeled, show numerous shallow sacculations that give the profile of the glandular epithelium a serrated appearance. This is one of the distinctive features of the secretory phase. It is seen most advantageously in areas where the plane of section is close to the long axis of the gland. In contrast to the characteristic sinuous course of the glands in the stratum functionale, glands of the stratum basale more closely resemble those in the proliferative phase. They are not oriented in any


Histology_Ross

Histology_Ross. to the characteristic sinuous course of the glands in the stratum functionale, glands of the stratum basale more closely resemble those in the proliferative phase. They are not oriented in any noticeable relationship to the uterine surface, and many of their long profiles are even parallel to the plane of the surface.


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Histology_Ross. Endometrium, secretory phase, uterus, human, H&E ×30; inset ×120. This slightly higher-magnification view of the stratum functionale shows essentially the same characteristics of the endometrial glands (Gl) described above; it also shows other modifications that occur during the secretory phase. One of these is that the endometrium becomes edematous. The increase in endometrial thickness because of edema is reflected by the presence of empty spaces between cells and other formed elements. Thus, many areas of this figure, especially the area within and near the rectangle, show histologic signs of edema. In addition, in this phase the glandular epithelial cells begin to secrete a mucoid fluid that is rich in glycogen. This product is secreted into the lumen of the glands, causing them to dilate. Typically, the glands of the secretory endometrium are more dilated than those of the proliferative endometrium.


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Histology_Ross. The rectangle in this figure highlights two glands that are shown at higher magnification in the inset. Each of these glands contains some substance within the lumen. The mucoid character of the substance within one of the glands can be surmised from its blue staining. Although not evident in routine H&E paraffin sections, the epithelial cells also contain glycogen during the secretory phase and as mentioned above, this becomes part of the secretion. The arrowheads indicate stromal cells; some of these cells undergo enlargement late in the secretory phase. These modified stromal cells, called decidual cells, play a role in implantation. Gl, endometrial glands M, myometrium SB, stratum basale SF, stratum functionale arrow, glandular opening at uterine surface arrowheads, stromal cells KEY


Histology_Ross

Histology_Ross. The cervix is the narrow or constricted inferior portion of the uterus, part of which projects into the vagina. The cervical canal traverses the cervix and provides a channel connecting the vagina and the uterine cavity. The structure of the cervix resembles the rest of the uterus in that it consists of a mucosa (endometrium) and a myometrium. There are, however, some important differences in the mucosa. The endometrium of the cervix does not undergo the cyclical growth and loss of tissue that is characteristic of the body and fundus of the uterus. Rather, the amount and character of the mucous secretion of its simple columnar epithelium vary at different times in the uterine cycle under the influence of the ovarian hormones. At midcycle, there is a 10-fold increase in the amount of mucus produced; this mucus is less viscous and provides a favorable environment for sperm migration. At other times in the cycle, the mucus restricts the passage of sperm into the uterus. The myometrium


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Histology_Ross. produced; this mucus is less viscous and provides a favorable environment for sperm migration. At other times in the cycle, the mucus restricts the passage of sperm into the uterus. The myometrium forms the major thickness of the cervix. It consists of interweaving bundles of smooth muscle cells in an extensive, continuous network of fibrous connective tissue.


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Histology_Ross. Cervix, uterus, human, H&E ×15. The portion of the cervix that projects into the vagina, the vaginal part or ectocervix, is represented by the upper two thirds of top figure. The lower third of the micrograph reveals the portion of the cervical canal (CC). Lower figure shows the continuation of cervical canal (CC). The plane of section in both figures passes through the long axis of the cervical canal which is narrowed and cone shaped at its two ends. The upper end, the internal os, communicates with the uterine cavity, and the lower end, the external os (Os), communicates with the vagina. (For purposes of orientation, realize that only one side of the longitudinal section of the cervix is shown in these Ectocervix, uterus, human, H&E ×240.


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Histology_Ross. Ectocervix, uterus, human, H&E ×240. The surface of the vaginal part of the cervix, ectocervix is covered by the stratified squamous epithelium (SSEp). The epithelium-connective tissue junction presents a relatively even contour in contrast to the irregular profile seen in the vagina. Transformation zone, cervix, uterus, human, H&E ×240. The mucosa of the cervical canal is covered with columnar epithelium. An abrupt change from stratified squamous epithelium (SSEp) to simple columnar epithelium (CEp) occurs within the transformation zone at the vaginal opening Cervical glands, cervix, uterus, human, H&E ×500.


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Histology_Ross. Cervical glands, cervix, uterus, human, H&E ×500. This figure shows, at high magnification, portions of the cervical gland identified in the rectangle in Figure on left. Note the tall epithelial cells and the lightly staining supranuclear cytoplasm, a reflection of the mucin dissolved out of the cell during figures and that the actual specimen, as seen in a section, would present a similar image on the other side of the cervical canal.) The mucosa (Muc) of the cervix differs according to the cavity it faces. The two rectangles in upper figure delineate representative areas of the mucosa that are shown at higher magnification in upper right and middle right figures, respectively. Bottom figure emphasizes the nature of the cervical glands (Gl). The glands differ from those of the uterus in that they branch extensively. They secrete a mucous substance into the cervical canal that serves to lubricate the vagina.


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Histology_Ross. In other respects, the epithelium has the same general features as the vaginal epithelium. Another similarity is that the epithelial surface of the ectocervix undergoes cyclical changes similar to those of the vagina in response to ovarian hormones. The mucosa of the ectocervix, like that of the vagina, is devoid of glands. of the cervical canal (external os). The lower rectangle in top left figure marks this site, known as the transition zone, which is shown at higher magnification here. Note the abrupt change in the epithelium at the point indicated by the diamond-shaped marker, as well as the large number of lymphocytes present in this region.


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Histology_Ross. tissue preparation. The crowding and the change in shape of the nuclei (asterisk) seen at the upper part of one of the glands in this figure are due to a tangential cut through the wall of the gland as it passed out of the plane of section. (It is not uncommon for cervical glands to develop into cysts as a result of obstruction in the duct. Such cysts are referred to as Nabothian cysts.) BV, blood vessels CC, cervical canal CEp, columnar epithelium Gl, cervical glands Muc, mucosa Os, ostium of the uterus SSEp, stratified squamous epithelium asterisk, tangential cut of the epithelial surface KEY


Histology_Ross

Histology_Ross. The placenta is a disc-shaped organ that serves for the exchange of materials between the fetal and maternal circulations during pregnancy. It develops primarily from embryonic tissue, the chorion frondosum. One side of the placenta is embedded in the uterine wall at the basal plate. The other side faces the amniotic cavity that contains the fetus. After birth, the placenta separates from the wall of the uterus and is discharged along with the contiguous membranes of the amniotic cavity. The umbilical cord connects the fetus to the placenta. It contains two arteries that carry blood from the fetus to the placenta and a vein that returns blood from the placenta to the fetus. The umbilical arteries have thick muscular walls. These are arranged as two layers, an inner longitudinal layer and an outer circular layer. Elastic lamellae are poorly developed in these vessels and, indeed, may be absent. The umbilical vein is similar to the arteries, also having a thick muscular wall arranged as


Histology_Ross

Histology_Ross. outer circular layer. Elastic lamellae are poorly developed in these vessels and, indeed, may be absent. The umbilical vein is similar to the arteries, also having a thick muscular wall arranged as an inner longitudinal and an outer circular layer.


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Histology_Ross. Placenta, human, H&E ×16. A section extending from the amniotic surface into the substance of the placenta is shown here. This includes the amnion (A), the chorionic plate (CP), and the chorionic villi (CV). The amnion consists of a layer of simple cuboidal epithelium and an underlying layer of connective tissue. The connective tissue of the amnion is continuous with the connective tissue of the chorionic plate as a result of their fusion at an earlier time. The plane of fusion, however, is not evident in H&E sections; the separation (asterisks) in parts of this figure in the vicinity of the fusion is an artifact.


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Histology_Ross. The chorionic plate is a thick connective tissue mass that contains the ramifications of the umbilical arteries and vein. These vessels (BVp) do not have the distinct organizational features characteristic of arteries and veins; rather, they resemble the vessels of the umbilical cord. Although their identification as blood vessels is relatively simple, it is difficult to distinguish which vessels are branches of an umbilical artery and which are tributaries of the vein.


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Histology_Ross. The main substance of the placenta consists of chorionic villi of different sizes (see Plate 100). These emerge from the chorionic plate as large stem villi that branch into increasingly smaller villi. Branches of the umbilical arteries and vein (BVv, in figure below) enter the stem villi and ramify through the branching villous network. Some villi extend from the chorionic plate to the maternal side of the placenta and make contact with the maternal tissue; these are called anchoring villi. Other villi, the free villi, simply arborize within the substance of the placenta without anchoring onto the maternal side. Placenta, human, H&E ×70; inset ×370.


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Histology_Ross. Placenta, human, H&E ×70; inset ×370. The maternal side of the placenta is shown in this figure. The basal plate, or stratum basale (SB), is on the right side of the illustration. This is the part of the uterus to which the chorionic villi anchor. Along with the usual connective tissue elements, the basal plate contains specialized cells called decidual cells (DC). The same cells are shown at higher magnification in the inset. Decidual cells are usually found in clusters and have an epithelial appearance. Because of these features, they are easily identified. Septa from the basal plate extend into the portion of the placenta that contains the chorionic villi. The septa do not contain the branches of the umbilical vessels and, on this basis, can frequently be distinguished from stem villi or their branches.


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Histology_Ross. PLATE 99 A, amnion BVp, blood vessels in chorionic plate BVv, blood vessels in chorionic villi CP, chorionic plate CV, chorionic villi DC, decidual cells SB, stratum basale asterisk, separation that is actually an artifact KEY


Histology_Ross

Histology_Ross. As the embryo develops, the invasive activity of the syncytiotrophoblast erodes the maternal capillaries and anastomoses them with the tro-phoblast lacunae, forming the maternal blood sinusoids. These communicate with each other and form a single blood compartment, lined by syn-cytiotrophoblasts, called the intervillous space. At the end of the second week of development, cytotrophoblast cells form primary chorionic villi. They project into the maternal blood space. In the third week of development, invasion of the extra embryonic mesenchyme into the primary chori-onic villi creates secondary chorionic villi. At the end of the third week, core mesenchyme differentiates into connective tissue and blood vessels that connect with the embryonic circulation. These tertiary chorionic villi constitute functional units for exchange of gases, nutrients, and waste products between maternal and fetal circulation without direct contact with each other. This separation of fetal and maternal blood


Histology_Ross

Histology_Ross. functional units for exchange of gases, nutrients, and waste products between maternal and fetal circulation without direct contact with each other. This separation of fetal and maternal blood is referred to as the placental barrier. Each tertiary villus consists of a connective tissue core surrounded by two distinct layers of trophoblast-derived cells. The outermost layer consists of the syncytiotrophoblast; immediately under it is a layer of cytotrophoblast cells. Starting at the fourth month, these lay-ers become very thin to facilitate the exchange of products across the placental barrier. The thinning of the wall of the villus is due to the loss of the inner, cytotrophoblastic layer. At this stage, the syncytiotrophoblast forms numerous trophoblastic buds that resemble the primary chorionic villi; however, the cytotrophoblast and the connective tissue grow very rapidly into these structures, transforming them into tertiary villi. At term, the placental barrier consists of the


Histology_Ross

Histology_Ross. chorionic villi; however, the cytotrophoblast and the connective tissue grow very rapidly into these structures, transforming them into tertiary villi. At term, the placental barrier consists of the syncytiotrophoblasts; a spare, discontinuous, inner cytotrophoblast layer; the basal lamina of the trophoblast; the connective tissue of the villus; the basal lamina of the endothelium; and the endothelium of the fetal placental capillary in the tertiary villus.


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Histology_Ross. Tertiary chorionic villi, placenta, full-term, human, H&E ×280. This photomicrograph shows a section through the intervillous space of the placenta at term. It includes chorionic villi (CV) of different sizes and the surrounding intervillous space (IS). The connective tissue of the villi contains branches and tributaries of the umbilical vein (UV) and arteries. The intervillous space usually contains maternal blood (only a few maternal blood cells are seen here). The outermost layer of each chorionic villus derives from the fusion of cytotrophoblast cells. This layer, known as the syncytiotrophoblast (S), has no intercellular boundaries, and its nuclei are rather evenly distributed, giving this layer an appearance similar to that of cuboidal epithelium. In some areas, nuclei are gathered in clusters (arrowheads); in other regions the Tertiary chorionic villi, placenta, mid-term, human, H&E ×320.


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Histology_Ross. This higher-magnification photomicrograph shows a cross section through immature chorionic tertiary villi surrounded by the intervillous space (IS). At this stage, chorionic villi are growing by proliferation of their core mesenchyme, syncy tiotrophoblast (S), and fetal endothelial cells. The syncytiotrophoblast syncytiotrophoblast layer appears relatively free of nuclei (arrows). These stretches of the syncytiotrophoblast may be so attenuated in places that the villous surface appears devoid of a covering. The syncytiotrophoblast contains microvilli that project into the intervillous space. In well-preserved specimens they may appear as a striated border (see inset below). The cytotrophoblast consists of an irregular layer of mono-nucleated cells that lies beneath the syncytiotrophoblast. In immature placentas, the cytotrophoblasts form an almost complete layer of cells. In this full-term placenta, only occasional cytotrophoblast cells (C) can be discerned. Most of the cells within


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Histology_Ross. In immature placentas, the cytotrophoblasts form an almost complete layer of cells. In this full-term placenta, only occasional cytotrophoblast cells (C) can be discerned. Most of the cells within the core of the villus are typical connective tissue fibroblasts and endothelial cells. Other cells have a visible amount of cytoplasm that surrounds the nucleus. These are considered to be fetal placental antigen–presenting cells or placental macrophages (PM) historically known as the Hofbauer cells.


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Histology_Ross. Secondary chorionic villi, placenta, human, H&E x320; inset ×640. This micrographs shows the secondary chorionic villi in the third week of embryonic development. These villi are composed of a mesenchymal core (MC) surrounded by two distinct layers of the trophoblast. Secondary villi have a much larger number of cytotrophoblast cells (C) than the mature tertiary villi and form an almost complete layer of cells immediately deep to the syncytiotrophoblast (S) (see inset). The syncytiotrophoblast covers not only the surface of the chorionic villi, but also extends into chorionic plate. Maternal red blood cells are present in the intervillous space.


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Histology_Ross. surrounding the chorionic villus (center of the image) forms trophoblastic bud (TB), which will be invaded subsequently by cells of the cytotrophoblast (C), connective tissue, and rapidly developing new blood vessels. In addition to fibroblasts, several fetal placental antigen–presenting cells (placental macrophages) (PM) can be identified by the amount of cytoplasm surrounding their nuclei. C, cytotrophoblast cells CV, chorionic villiI S, intervillous space MC, mesenchymal core PM, placental macrophages S, syncytiotrophoblast TB, trophoblastic bud UV, umbilical vein KEY


Histology_Ross

Histology_Ross. The vagina is the fibromuscular tube of the female reproductive tract that leads to the exterior of the body. The wall of the vagina consists of three layers: a mucosa, a muscularis, and an adventitia. The epithelium of the mucosa is nonkeratinized stratified squamous. It undergoes changes that correspond to the ovarian cycle. The amount of glycogen stored in the epithelial cells increases under the influence of estrogen, whereas the rate of desquamation increases under the influence of progesterone. The glycogen liberated from the desquamated cells is fermented by lactobacilli vaginalis, producing lactic acid that acidifies the vaginal surface and inhibits colonization by yeasts and potentially harmful bacteria. The vagina has certain histologic similarities to the proximal portion of the alimentary canal but is distinguished by the following features: The epithelium does not keratinize, and except for the deepest layers, the cells appear to be empty in routine H&E sections; the


Histology_Ross

Histology_Ross. the alimentary canal but is distinguished by the following features: The epithelium does not keratinize, and except for the deepest layers, the cells appear to be empty in routine H&E sections; the mucosa contains neither glands nor a muscularis mucosae; the muscle is smooth and not well ordered. This should be contrasted with the oral cavity, pharynx, and upper part of the esophagus in which the muscle is striated. The more distal portion of the esophagus, which contains smooth muscle, can be distinguished easily from the vagina because it has a muscularis mucosae.


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Histology_Ross. Vagina, human, H&E ×90. The mucosa of the vagina consists of a stratified squamous epithelium (Ep) and an underlying fibrous connective tissue (CT) that often appears more cellular than other fibrous connective tissue. The boundary between the two is readily identified because of the conspicuous staining of the closely packed small cells of the basal layer (B) of the epithelium. Connective tissue papillae project into the underside of the epithelium, giving the epithelial– connective tissue junction an uneven appearance. The papillae may be cut obliquely or in cross section and thus may appear as connective tissue islands (arrows) within the lower portion of the epithelium. The epithelium is characteristically thick and although keratohyaline granules may be found in the Mucosa, vagina, human H&E ×110.


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Histology_Ross. Mucosa, vagina, human H&E ×110. This is a higher magnification of the epithelium that includes the area outlined by the rectangle in upper figure (turned 90 ). The obliquely cut and cross-sectioned portions of connective tissue papillae that appear as connective tissue islands in the Mucosa, vagina, human H&E ×225. This is a higher-magnification micrograph of the basal portion of the epithelium (Ep) between connective tissue papillae. Note the regularity and dense packing of the basal epithelial cells. They are the stem cells for the stratified squamous epithelium. Daughter cells of these cells migrate toward the surface Muscularis, vagina, human, H&E ×125. This higher-magnification micrograph of the smooth muscle of the vaginal wall emphasizes the irregularity of the arrangement of the muscle bundles. At the right edge of the figure is a bundle of smooth muscle cut in a longitudinal section (SML).


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Histology_Ross. superficial cells, keratinization does not occur in human vaginal epithelium. Thus, nuclei can be observed throughout the entire thickness of the epithelium despite the fact that the cytoplasm of most of the cells above the basal layers appears empty. These cells are normally filled with large deposits of glycogen that is lost in the processes of fixation and embedding of the tissue. The rectangle outlines a portion of the epithelium and connective tissue papillae that is examined at higher magnification below. The muscular layer of the vaginal wall consists of smooth muscle arranged in two ill-defined layers. The outer layer is generally said to be longitudinally arranged (SML), and the inner layer is generally said to be circularly arranged (SMC), but the fibers are more usually organized as interlacing bundles surrounded by connective tissue. Many blood vessels (BV) are seen in the connective tissue.


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Histology_Ross. epithelium are more clearly seen here (arrows), in some instances outlined by the surrounding closely packed cells of the basal epithelial cell layer. Note, again, that the epithelial cells even at the surface still retain their nuclei and there is no evidence of keratinization. and begin to accumulate glycogen and become less regularly arranged as they move toward the surface. The highly cellular connective (CT) tissue immediately beneath the basal layer (B) of the epithelium typically contains many lymphocytes (L). The number of lymphocytes varies with the stage of the ovarian cycle. Lymphocytes invade the epithelium around the time of menstruation and appear along with the epithelial cells in vaginal smears.


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Histology_Ross. Adjacent to this is a bundle of smooth muscle cut in cross section (SMC). This bundle abuts on a longitudinally sectioned lymphatic vessel (LV). To the left of the lymphatic vessel is another longitudinal bundle of smooth muscle (SML). A valve (Va) is seen in the lymphatic vessel. A small vein (V) is present in the circular smooth muscle close to the lymphatic. B, basal layer of vaginal epithelium BV, blood vessels CT, connective tissue Ep, epithelium L, lymphocytes LV, lymphatic vessel SMC, smooth muscle, cross section SML, smooth muscle, longitudinal section V, vein Va, valve in lymphatic vessel arrows, connective tissue islands in epithelium KEY


Histology_Ross

Histology_Ross. The mammary glands are branched tubuloalveolar glands that develop from epidermis and come to lie in the subcutaneous tissue (superficial fascia). They begin to develop at puberty in the female but do not reach a fully functional state until after pregnancy. The glands also develop in the male at puberty; the development is limited, however, and the glands usually remain in a stabilized state. Mammary gland, inactive stage, human, H&E ×80. This figure is a section through an inactive gland. The parenchyma is sparse and consists mainly of duct elements. Several ducts (D) are shown in the center of the field. A small lumen can be seen in each. The ducts are surrounded by a loose Mammary gland, inactive stage, human, H&E ×200; inset ×400.


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Histology_Ross. Additional details are evident at higher magnification. In distinguishing between the loose and dense connective tissue, recall that both extracellular and cellular features show differences that are evident in both the figure and the inset. Note the thicker collagenous fibers in the dense connective tissue in contrast to the much thinner fibers of the loose connective tissue. The loose connective tissue contains far more cells per unit area and a greater variety of cell types. This figure shows a cluster of lymphocytes (L) and, at still higher magnification (inset), plasma cells (P) and individual lymphocytes (L). Both plasma cells and lymphocytes are cells with a rounded shape, but plasma cells are larger and show more cytoplasm. In addition, regions of plasma cell cytoplasm display basophilia. Elongate nuclei in spindle-shaped cells belong to fibroblasts. In con- connective tissue (see CT(L), in figure below, and together, the ducts and surrounding connective tissue constitute a


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Histology_Ross. Elongate nuclei in spindle-shaped cells belong to fibroblasts. In con- connective tissue (see CT(L), in figure below, and together, the ducts and surrounding connective tissue constitute a lobule. Two terminal duct lobular units (TDLU) are bracketed in this figure. Beyond the lobular unit, the connective tissue is more dense (CT(D)). The two types of connective tissues can be distinguished at the low magnification of this figure.


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Histology_Ross. trast, although the cell types in the dense connective tissue may also be diverse, a simple examination of equal areas of loose and dense connective tissue will, by far, show fewer cells in the dense connective tissue. Characteristically, the dense connective tissue contains numerous aggregates of adipocytes (A).


Histology_Ross

Histology_Ross. The epithelial cells within the resting lobular units are regarded as being chiefly duct elements. Usually, alveoli are not found; their precursors, however, are represented as cellular thickenings of the duct wall. The epithelium of the resting lobule is cuboidal; in addition, myoepithelial cells are present. Reexamination of the inset shows a thickening of the epithelium in one location, presumably the precursor of an alveolus, and myoepithelial cells (M) at the base of the epithelium. As elsewhere, the myoepithelial cells are on the epithelial side of the basement membrane. During pregnancy, the glands begin to proliferate. This can be thought of as a dual process in which ducts proliferate and alveoli grow from the ducts. MAM MARY G LAN D I NACTIVE STAG E A, adipocytes CT(D), dense connective tissue CT(L), loose connective tissue D, ducts L, lymphocytes M, myoepithelial cells P, plasma cells TDLU, terminal duct lobular unit KEY


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Histology_Ross. PLATE 103 Mammary Gland, Late Proliferative and Lactating Stages


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Histology_Ross. Mammary glands exhibit a number of changes during pregnancy in preparation for lactation. Lymphocytes and plasma cells infiltrate the loose connective tissue as the glandular tissue develops. As the cells of the glandular portion proliferate by mitotic division, the ducts branch and alveoli begin to develop at their growing ends. Alveolar development becomes most prominent in the later stages of pregnancy, and accumulation of secretory product takes place in the alveoli. At the same time, lymphocytes and plasma cells become prominent in the loose connective tissue of the developing lobules. Myoepithelial cells proliferate between the base of the epithelial cells and the basal lamina in both the alveolar and the ductal portion of the glands. They are most prominent in the larger ducts. Both merocrine and apocrine secretion are involved in the production of milk. The protein component is synthesized, concentrated, and secreted by exocytosis in a manner typical for protein secretion. The


Histology_Ross

Histology_Ross. merocrine and apocrine secretion are involved in the production of milk. The protein component is synthesized, concentrated, and secreted by exocytosis in a manner typical for protein secretion. The lipid component begins as droplets in the cytoplasm that coalesce into large droplets in the apical cytoplasm of the alveolar cells and cause the apical plasma membrane to bulge into the alveolar lumen. The droplets are surrounded by a thin layer of cytoplasm and are enveloped in plasma membrane as they are released. The initial secretion in the first days after birth is called colostrum. This premilk is an alkaline secretion with a higher protein, vitamin A, sodium, and chloride content than milk and a lower lipid, carbohydrate, and potassium content. Considerable amounts of antibodies are contained in colostrum, and these provide the newborn with passive immunity to many antigens. The antibodies are produced by the plasma cells in the stroma of the breast and are carried across the


Histology_Ross

Histology_Ross. contained in colostrum, and these provide the newborn with passive immunity to many antigens. The antibodies are produced by the plasma cells in the stroma of the breast and are carried across the glandular cells in a manner similar to that for secretory IgA in the salivary glands and intestine. A few days after parturition, the secretion of colostrum stops and lipid-rich milk is produced.


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Histology_Ross. PLATE 103 • MAMMARY GLAND, LATE PROLIFERATIVE AND LACTATING STAGES Mammary gland, late proliferative stage, human, H&E ×90; inset ×560. Whereas the development of the duct elements in the mammary gland occurs during the early proliferative stage, the development of the alveolar elements becomes conspicuous in the late proliferative stage. This figure shows the terminal duct lobular units (TDLU) at the late proliferative stage. Individual lobular units are separated by narrow dense connective tissue septa (S). The connective tissue within the lobular unit is a typical loose connective tissue that is now more cellular, containing mostly plasma cells and lymphocytes. The alveoli are well developed, and many exhibit precipitated secretory product. Each of the alveoli is joined to a duct, although that relationship can be difficult to identify. The epithelium of the intralobular ducts is similar in Mammary gland, lactating stage, human, methyl green-osmium ×90; inset ×700.


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Histology_Ross. The specimen shown here is from a lactating mammary gland. It is similar in appearance to the gland at the late proliferative stage but differs mainly to the extent that the alveoli are more uniform in appearance and their lumina are larger. As in the late proliferative stage, several alveoli can be seen merging with one another (asterisks). The use of osmium in this specimen stains the lipid component of the secretion. The inset reveals the lipid droplets within the epithelial cell cytoplasm as well as lipid that has been secreted into the lumen appearance to the alveolar epithelium. The cells of both components are secretory. The alveoli as well as the intralobular ducts consist of a single layer of cuboidal epithelial cells subtended by myoepithelial cells. Often, what appear to be several alveoli are seen merging with one another (asterisks). Such profiles represent alveolar units opening into a duct. Interlobular ducts are easy to identify as they are surrounded by dense


Histology_Ross

Histology_Ross. be several alveoli are seen merging with one another (asterisks). Such profiles represent alveolar units opening into a duct. Interlobular ducts are easy to identify as they are surrounded by dense connective tissue. In one instance, an intralobular duct can be seen emptying into an interlobular duct (arrow). The inset shows the secretory epithelium at a much higher magnification. Note that it is a simple columnar epithelium. The nucleus of a myoepithelial cell (M) is seen at the base of the epithelium. Generally, these cells are difficult to recognize. Also, as noted above, numerous plasma cells (P) and lymphocytes (Ly) are present in the loose connective tissue of the lobule.


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Histology_Ross. of the alveolus. The lipid first appears as small droplets within the epithelial cells. These droplets become larger and ultimately are secreted into the alveolar lumen along with milk proteins. The milk proteins are present in small vacuoles in the apical part of the cell but cannot be seen by light microscopic methods. They are secreted by exocytosis. The lipid droplets, in contrast, are large and surrounded by the apical cell membrane as they are pinched off to enter the lumen; thus it is an apocrine secretion. Several interlobular ducts are evident. One of these ducts reveals a small branch, an ending intralobular duct (arrows) joining the interlobular duct. D, interlobular duct Ly, lymphocyte M, myoepithelial cell P, plasma cell S, connective tissue septa TDLU, terminal duct lobular unit arrow, union of intralobular duct with interlobular duct asterisks, sites of merging alveoli KEY


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Histology_Ross. PLATE 103 • MAMMARY GLAND, LATE PROLIFERATIVE AND LACTATING STAGES TDLUTDLUTDLU TDLUTDLUTDLU TDLUTDLUTDLU DDD MMM *** *** *** *** *** *** *** *** DDDDD DDDD LyLyPPLy P SSS SSS OVERVIEW OF THE EYE / 896 GENERAL STRUCTURE OF THE EYE / 896 Layers of the Eye / 896 Chambers of the Eye / 897 Development of the Eye / 898 MICROSCOPIC STRUCTURE OF THE EYE / 899 Corneoscleral Coat / 899 Vascular Coat (Uvea) / 902 Retina / 907 Crystalline Lens / 915 Vitreous Body / 915 Accessory Structures of the Eye / 916 Folder 24.1 Clinical Correlation: Glaucoma / 905 Folder 24.2 Clinical Correlation: Retinal Detachment / 908 Folder 24.3 Clinical Correlation: Age-Related Macular Degeneration (ARMD) / 909 Folder 24.4 Clinical Correlation: Conjunctivitis / 917


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Histology_Ross. The eye is a complex sensory organ that provides the sense of sight. In many ways, the eye is similar to a digital camera. Like the optical system of a camera, the cornea and lens of the eye capture and automatically focus light. The iris also automatically adjusts the eye to differences in illumination of visual fields. In many aspects, the optical system of the eye is far more elaborate and complex than a camera. For example, the eye has the ability to track moving objects with coordinated eye movements. The eye can also protect, maintain, self-repair, and clean its transparent optical system. The light detector in a digital camera, the charge-coupled device (CCD), consists of closely spaced photodiodes that capture, collect, and convert the light image into a series of electrical impulses. Similarly, the photoreceptor cells in the retina of the eye detect light intensity and color (wavelengths of visible light that are reflected by different objects) and encode these parameters


Histology_Ross

Histology_Ross. Similarly, the photoreceptor cells in the retina of the eye detect light intensity and color (wavelengths of visible light that are reflected by different objects) and encode these parameters into electrical impulses for transmission to the brain via the optic nerve. The retina has other capabilities beyond those of a CCD: It can extract and modify specific impulses from the visual image before sending them to the central nervous system (CNS).


Histology_Ross

Histology_Ross. Because the eyes are paired, two somewhat different and overlapping images (visual fields) are sent to the brain. The brain can be compared to a computer, which processes the slightly different images from each eye, separates them into layers, and projects them onto the primary visual cortex located in the occipital lobes. Complex neural mechanisms coordinate eye movements, enabling us to perceive depth and distance to achieve a three-dimensional image. Therefore, the way in which we perceive the world around us largely depends on impulses processed within the retina and analysis and interpretation of these impulses by the CNS. The eye measures approximately 25 mm in diameter. It is suspended in the bony orbital socket by six extrinsic muscles that control its movement. A thick layer of adipose tissue partially surrounds and cushions the eye as it moves within the orbit. The extraocular muscles are coordinated so that the eyes move symmetrically around their own central axes.


Histology_Ross

Histology_Ross. Layers of the Eye The wall of the eye consists of three concentric layers or coats. The eyeball is composed of three structural layers (Fig. 24.1):  The corneoscleral coat, the outer or fibrous layer, includes the sclera, the white portion, and the cornea, the transparent portion. FIGURE 24.1 • Schematic diagram of the layers of the eye. The wall of the eyeball is organized in three separate concentric layers: (a) an outer supporting layer, the corneoscleral coat (colorless and blue); (b) a middle vascular coat or uvea (pink); and (c) an inner photosensitive layer, the retina (yellow).  The vascular coat, the middle layer, or uvea, includes the choroid and the stroma of the ciliary body and iris.  The retina, the inner layer, includes an outer pigment ep ithelium, the inner neural retina, and the epithelium of the ciliary body and iris. The neural retina is continuous with the central nervous system through the optic nerve.


Histology_Ross

Histology_Ross. The corneoscleral coat consists of the transparent cornea and the white opaque sclera. The cornea covers the anterior one-sixth of the eye (Fig. 24.1a). In this windowlike region, the surface of the eye has a prominence or convexity. The cornea is continuous with the sclera (Gr. skleros, hard). The sclera is composed of dense fibrous connective tissue that provides attachment for the extrinsic muscles of the eye. The sclera constitutes the “white” of the eye. In children, it has a slightly blue tint because of its thinness; in elderly people, it is yellowish because of the accumulation of lipofuscin in its stromal cells. The corneoscleral coat encloses the inner two layers except where it is penetrated by the optic nerve. The uvea consists principally of the choroid, the vascular layer that provides nutrients to the retina.


Histology_Ross

Histology_Ross. The uvea consists principally of the choroid, the vascular layer that provides nutrients to the retina. Blood vessels and melanin pigment give the choroid an intense dark brown color. The pigment absorbs scattered and reflected light to minimize glare within the eye. The choroid contains many venous plexuses and layers of capillaries and is firmly attached to the retina (Fig. 24.1b). The anterior rim of the uveal layer continues forward, where it forms the stroma of the ciliary body and iris. The ciliary body is a ringlike thickening that extends inward just posterior to the level of the corneoscleral junction. Within the ciliary body is the ciliary muscle, a smooth muscle that is responsible for lens accommodation. Contraction of the ciliary muscle changes the shape of the lens, which enables it to bring light rays from different distances to focus on the retina.


Histology_Ross

Histology_Ross. The iris is a contractile diaphragm that extends over the anterior surface of the lens. It also contains smooth muscle and melanin-containing pigment cells scattered in the connective tissue. The pupil is the central circular aperture of the iris. It appears black because one looks through the lens toward the heavily pigmented back of the eye. In the process of adaptation, the pupil changes in size to control the amount of light that passes through the lens to reach the retina. The retina consists of two components: The neural retina and pigment epithelium. The retina is a thin, delicate layer (Fig. 24.1c) consisting of two components:  The neural retina is an inner layer that contains light-sensitive receptors and complex neuronal networks.  The retinal pigment epithelium (RPE) is an outer layer composed of simple cuboidal melanin-containing cells.


Histology_Ross

Histology_Ross. Externally, the retina rests on the choroid; internally, it is associated with the vitreous body. The neural retina consists largely of photoreceptor cells, called retinal rods and cones, and interneurons. Visual information encoded by the rods and cones is sent to the brain via impulses conveyed along the optic nerve. Chambers of the Eye The layers of the eye and the lens serve as boundaries for three chambers within the eye. The chambers of the eye are the following.  The anterior chamber is the space between the cornea and the iris.  The posterior chamber is the space between the posterior surface of the iris and the anterior surface of the lens.  The vitreous chamber is the space between the posterior surface of the lens and the neural retina (Fig. 24.2). The cornea, the anterior and posterior chambers, and their contents constitute the anterior segment of the eye. The


Histology_Ross

Histology_Ross. FIGURE 24.2 • Schematic diagram canal of illustrating the internal structures of the human eye. The retina consists of that differ in their function. Note that the photosensitive region of the retina occupies the posterior part of the eye and terminates iris anteriorly along the ora serrata. The nonphotosensitive region of the retina is located anterior to the ora serrata and lines the inner aspect of the ciliary body and the posterior surface of the iris. The other layers of the eyeball as well as the attachment of two of the extraocular muscles to the sclera inferior rectus muscle are also shown. vitreous chamber, visual retina, RPE, posterior sclera, and Development of the Eye uvea constitute the posterior segment. To appreciate the unusual structural and functional relationships in the eye, it is helpful to understand how it forms in the The refractile media components of the eye alter the light embryo. path to focus it on the retina.


Histology_Ross

Histology_Ross. The refractile media components of the eye alter the light embryo. path to focus it on the retina. As light rays pass through the components of the eye, they are The tissues of the eye are derived from neuroectoderm, refracted. Refraction focuses the light rays on the photorecep surface ectoderm, and mesoderm. tor cells of the retina. Four transparent components of the By the 22nd day of development, the eyes are evident as eye, called the refractile (or dioptric) media, alter the path shallow grooves—the optic sulci or grooves—in the neural of the light rays: folds at the cranial end of the human embryo. As the neural  The cornea is the anterior window of the eye. tube closes, the paired grooves form outpocketings called optic The aqueous humor is the watery fluid located in the vesicles (Fig. 24.3a). As each optic vesicle grows laterally, the anterior and posterior chambers.


Histology_Ross

Histology_Ross. connection to the forebrain becomes constricted into an optic  The lens is a transparent, crystalline, biconcave structure stalk, and the overlying surface ectoderm thickens and forms a suspended from the inner surface of the ciliary body by a lens placode. These events are followed by concomitant in-ring of radially oriented fibers, the zonule of Zinn. vagination of the optic vesicles and the lens placodes. The in The vitreous body is composed of a transparent gel subvagination of the optic vesicle results in the formation of a stance that fills the vitreous chamber. It acts as a “shock double-layered optic cup (Fig. 24.3b). The inner layer becomes absorber” that protects the fragile retina during rapid eye the neural retina. The outer layer becomes the RPE. movement and helps to maintain the shape of the eye.


Histology_Ross

Histology_Ross. movement and helps to maintain the shape of the eye. Invagination of the central region of each lens placode re-The vitreous body is almost 99% water with soluble prosults in the formation of the lens vesicles. By the fifth week teins, hyaluronan, glycoproteins, widely dispersed collaof development, the lens vesicle loses contact with the surface gen fibrils, and traces of other insoluble proteins. The ectoderm and comes to lie in the mouth of the optic cup. fluid component of the vitreous body is called the vitre-After the lens vesicle detaches from the surface ectoderm, this ous humor.


Histology_Ross

Histology_Ross. same site again thickens to form the corneal epithelium. Mes-The cornea is the chief refractive element of the eye. It has a enchymal cells from the periphery then give rise to the refractive index of 1.376 (air has a refractive index of 1.0). corneal endothelium and the corneal stroma. The lens is second in importance to the cornea in the refrac-Grooves containing blood vessels derived from mesenchyme tion of light rays. Because of its elasticity, the shape of the lens develop along the inferior surface of each optic cup and stalk. can undergo slight changes in response to the tension of the Called the choroid fssures, the grooves enable the hyaloid ciliary muscle. These changes are important in accommoda-artery to reach the inner chamber of the eye. This artery and its tion for proper focusing on near objects. The aqueous humor branches supply the inner chamber of the optic cup, lens vesicle, and vitreous body have only minor roles in refraction. How-and mesenchyme within the optic


Histology_Ross

Histology_Ross. on near objects. The aqueous humor branches supply the inner chamber of the optic cup, lens vesicle, and vitreous body have only minor roles in refraction. How-and mesenchyme within the optic cup. The hyaloid vein returns ever, the aqueous humor plays an important role in providing blood from these structures. The distal portions of the hyaloid nutrients to two avascular structures, the lens and cornea. In vessels degenerate, but the proximal portions remain as the cenaddition to transmitting light, the vitreous body helps main-tral retinal artery and central retinal vein. By the end of the tain the position of the lens and helps keep the neural retina seventh week, the edges of the choroid fissure fuse, and a round in contact with the RPE. opening, the future pupil, forms over the lens vesicle.


Histology_Ross

Histology_Ross. forebrain of optic cup lumen of choroid inner layer of optic nerveoptic stalk FIGURE 24.3 • Schematic drawing illustrating the development of the eye. a. Forebrain and developing optic vesicles as seen in a 4-mm embryo. b. Bilayered optic cup and invaginating lens vesicle as seen in a 7.5-mm embryo. The optic stalk connects the developing eye to the brain. c. The eye as seen in a 15-week fetus. All the layers of the eye are established, and the hyaloid artery traverses the vitreous body from the optic disc to the posterior surface of the lens. (Modified from Mann IC. The Development of the Human Eye. New York: Grune & Stratton, 1974.)


Histology_Ross

Histology_Ross. Human Eye. New York: Grune & Stratton, 1974.) The outer layer of the optic cup forms a single layer of pigmented cells (Fig. 24.3c). Pigmentation begins at the end of the fifth week. The inner layer undergoes a complex differentiation into the nine layers of the neural retina. The photoreceptor cells (rods and cones), as well as the bipolar, amacrine, and ganglion cells and nerve fibers are present by the seventh month. The macular depression begins to develop during the eighth month and is not complete until about 6 months after birth.


Histology_Ross

Histology_Ross. During the third month, growth of the optic cup gives rise to the ciliary body and the future iris, which forms a double row of epithelium in front of the lens. The mesoderm located external to this region becomes the stroma of the ciliary body and iris. Both epithelial layers of the iris become pigmented. In the ciliary body, however, only the outer layer is pigmented. At birth, the iris is light blue in fair-skinned people because pigment is usually not present. The dilator and sphincter pupillary muscles develop during the sixth month as derivatives of the neuroectoderm of the outer layer of the optic cup. The embryonic origins of the individual eye structures are summarized in Table 24.1. The cornea consists of five layers: Three cellular layers and two noncellular layers.


Histology_Ross

Histology_Ross. The embryonic origins of the individual eye structures are summarized in Table 24.1. The cornea consists of five layers: Three cellular layers and two noncellular layers. The transparent cornea (see Figs. 24.1 and 24.2) is only 0.5 mm thick at its center and about 1 mm thick peripherally. It consists of three cellular layers that are distinct in both appearance and origin. These layers are separated by two important membranes that appear homogeneous when viewed in the light microscope. Thus, the fve layers of the cornea seen in a transverse section are the following:


Histology_Ross

Histology_Ross. TABLE Embryonic Origins of the Individual Structures of the Eye24.1 Source Derivative Surface ectoderm Lens Epithelium of the cornea, conjunctiva, and lacrimal gland and its drainage system Neural ectoderm Vitreous body (derived partly from neural ectoderm of the optic cup and partly from mesenchyme) Epithelium of the retina, iris, and ciliary body Sphincter pupillae and dilator papillae muscles Optic nerve Mesoderm Sclera Stroma of the cornea, ciliary body, iris, and choroid Extraocular muscles Eyelids (except epithelium and conjunctiva) Hyaloid system (most of which degenerates before birth) Coverings of the optic nerve Connective tissue and blood vessels of the eye, bony orbit, and vitreous body The corneal epithelium is a nonkeratinized stratified squamous epithelium.


Histology_Ross

Histology_Ross. The corneal epithelium is a nonkeratinized stratified squamous epithelium. The corneal epithelium (Fig. 24.4) consists of approximately five layers of nonkeratinized cells and measures about 50 m in average thickness. It is continuous with the conjunctival epithelium that overlies the adjacent sclera. The epithelial cells adhere to neighboring cells via desmosomes that are present on short interdigitating processes. Like other stratified epithelium, such as that of the skin, the cells proliferate from a basal layer and become squamous at the surface. The basal cells are low columnar with round, ovoid nuclei; the surface cells acquire a squamous or discoid shape, and their nuclei are flattened and pyknotic (see Fig. 24.4b). As the cells migrate to the surface, the cytoplasmic organelles gradually disappear, indicating a progressive decline in metabolic activity. The corneal epithelium has a remarkable regenerative capacity with a turnover time of approximately 7 days.


Histology_Ross

Histology_Ross. The actual stem cells for the corneal epithelium reside at the corneoscleral limbus, the junction of the cornea and sclera. The microenvironment of this stem cell niche is important in maintaining the population of stem cells that also act as a “barrier” to conjunctival epithelial cells and normally prevent their migration to the corneal surface. The corneal epithelial stem cells may be partially or totally depleted by disease or extensive injury, resulting in abnormalities of the corneal surface that lead to conjunctivalization of the cornea, which is characterized by vascularization, appearance of goblet cells, and an irregular and unstable epithelium. These changes cause ocular discomfort and reduced vision. Minor injuries of the corneal surface heal rapidly by inducing stem cell proliferation and migration of cells from the corneoscleral limbus to fll the defect. Numerous free nerve endings in the corneal epithelium provide it with extreme sensitivity to touch. Stimulation of


Histology_Ross

Histology_Ross. FIGURE 24.4 • Photomicrograph of the cornea. a. This photomicrograph of a section through the full thickness of the cornea shows the corneal stroma and the two corneal surfaces covered by different types of epithelia. The corneal stroma does not contain blood or lymphatic vessels. 140. b. A higher magnification of the anterior surface of the cornea showing the corneal stroma covered by a stratified squamous (corneal) epithelium. The basal cells that rest on Bowman’s membrane, which is a homogeneous condensed layer of corneal stroma, are low columnar in contrast to the squamous surface cells. Note that one of the surface cells is in the process of desquamation (arrow). 280. c. A higher-magnification photomicrograph of the posterior surface of the cornea covered by a thin layer of simple squamous epithelium (corneal endothelium). These cells are in direct contact with the aqueous humor of the anterior chamber of the eye. Note the very thick Descemet’s membrane (basal lamina) of the


Histology_Ross

Histology_Ross. squamous epithelium (corneal endothelium). These cells are in direct contact with the aqueous humor of the anterior chamber of the eye. Note the very thick Descemet’s membrane (basal lamina) of the corneal endothelial cells. 280.


Histology_Ross

Histology_Ross. these nerves (e.g., by small foreign bodies) elicits blinking of the eyelids, flow of tears, and, sometimes, severe pain. Microvilli present on the surface epithelial cells help retain the tear film over the entire corneal surface. Drying of the corneal surface may cause ulceration. DNA in corneal epithelial cells is protected from UV light damage by nuclear ferritin. Despite constant exposure of the corneal epithelium to UV light, cancer of this epithelium is extremely rare. Unlike the epidermis, which is also exposed to UV light, melanin is not present as a defense mechanism in corneal epithelium. The presence of melanin in the cornea would diminish light transmission. Instead, it has recently been shown that corneal epithelial cell nuclei contain ferritin, an iron-storage protein. Experimental studies with avian corneas have shown that nuclear ferritin protects the DNA in the corneal epithelial cells from free radical damage caused by UV light exposure.


Histology_Ross

Histology_Ross. Bowman’s membrane is a homogeneous-appearing layer on which the corneal epithelium rests. Bowman’s membrane (anterior basement membrane) is a homogeneous, faintly fibrillar lamina that is approximately 8 m to 10 m thick. It lies between the corneal epithelium and the underlying corneal stroma and ends abruptly at the corneoscleral limbus. The collagen fibrils of Bowman’s membrane have a diameter of about 18 nm and are randomly oriented. Bowman’s membrane imparts some strength to the cornea, but more signifcantly, it acts as a barrier to the spread of infections. It does not regenerate. Therefore, if damaged, an opaque scar forms that may impair vision. In addition, changes in Bowman’s membrane are associated with recurrent corneal erosions. The corneal stroma constitutes 90% of the corneal thickness.


Histology_Ross

Histology_Ross. The corneal stroma constitutes 90% of the corneal thickness. The corneal stroma, also called substantia propria, is composed of about 60 thin lamellae. Each lamella consists of parallel bundles of collagen fibrils. Located between lamellae are nearly complete sheets of slender, flattened fibroblasts. The fibrils measure approximately 23 nm in diameter and are as long as 1 cm. The collagen fibrils in each lamella are arranged at approximately right angles to those in the adjacent lamellae (Fig. 24.5). The ground substance contains corneal proteoglycans, which are sulfated glycosaminoglycans— chiefly, keratan sulfate (lumican) and chondroitin sulfate covalently bound to protein (decorin). Lumican regulates normal collagen fibril assembly in the cornea and is critical in the development of a highly organized collagenous matrix.


Histology_Ross

Histology_Ross. It is believed that the uniform spacing of collagen fibrils and lamellae, as well as the orthogonal array of the lamellae (alternating layers at right angles), is responsible for the transparency of the cornea. Proteoglycans (lumican), along with type V collagen, regulate the precise diameter and spacing of the collagen fibrils. Swelling of the cornea after injury to the epithelium or endothelium disrupts this precise array and leads to translucency or opacity of the cornea. Lumican is FIGURE 24.5 • Electron micrograph of the corneal stroma. This electron micrograph shows parts of three lamellae and a portion of a corneal fibroblast (CF) between two of the lamellae. Note that the collagen fibrils in adjacent lamellae are oriented at right angles to one another. 16,700. overexpressed during the wound-healing process following corneal injury.


Histology_Ross

Histology_Ross. overexpressed during the wound-healing process following corneal injury. Normally, the cornea contains no blood vessels or pigments. During an infammatory response involving the cornea, large numbers of neutrophilic leukocytes and lymphocytes migrate from blood vessels of the corneoscleral limbus and penetrate the stromal lamellae. Descemet’s membrane is an unusually thick basal lamina. Descemet’s membrane (posterior basement membrane) is the basal lamina of corneal endothelial cells. It is intensely positive to periodic acid–Schiff (PAS) and can be as thick as 10 m. Descemet’s membrane has a feltlike appearance and consists of an interwoven meshwork of fibers and pores. It separates the corneal endothelium from the adjacent corneal stroma. Unlike Bowman’s membrane, Descemet’s membrane readily regenerates after injury. It is produced continuously but slowly thickens with age.


Histology_Ross

Histology_Ross. Unlike Bowman’s membrane, Descemet’s membrane readily regenerates after injury. It is produced continuously but slowly thickens with age. Descemet’s membrane extends peripherally beneath the sclera as a trabecular meshwork forming the pectinate ligament. Strands from the pectinate ligament penetrate the ciliary muscle and sclera and may help to maintain the normal curvature of the cornea by exerting tension on Descemet’s membrane. The corneal endothelium provides for metabolic exchange between the cornea and aqueous humor.


Histology_Ross

Histology_Ross. The corneal endothelium provides for metabolic exchange between the cornea and aqueous humor. The corneal endothelium is a single layer of squamous cells covering the surface of the cornea that faces the anterior chamber (see Fig. 24.4). The cells are joined by well-developed zonulae adherentes, relatively leaky zonulae occludentes, and desmosomes. Virtually all of the metabolic exchanges of the cornea occur across the endothelium. The endothelial cells contain many mitochondria and vesicles and an extensive rough-surfaced endoplasmic reticulum (rER) and Golgi apparatus. They demonstrate endocytotic activity and are engaged in active transport. Na/K-activated ATPase is located on the lateral plasma membrane.


Histology_Ross

Histology_Ross. Transparency of the cornea requires precise regulation of the water content of the stroma. Physical or metabolic damage to the endothelium leads to rapid corneal swelling and, if the damage is severe, corneal opacity. Restoration of endothelial integrity is usually followed by deturgescence, although corneas can swell beyond their ability for self-repair. Such swelling can result in permanent focal opacities caused by aggregation of collagen fbrils in the swollen cornea. Essential sulfated glycosaminoglycans that normally separate the corneal collagen fbers are extracted from the swollen cornea.


Histology_Ross

Histology_Ross. Human corneal endothelium has a limited proliferative capacity. Severely damaged endothelium can only be repaired by transplantation of a donor cornea. Recent studies indicate that the periphery of the cornea represents a regenerative zone of the corneal endothelial cells. However, soon after corneal transplantation, endothelial cells exhibit contact inhibition when exposed to the extracellular matrix of Descemet’s membrane. This fnding that inhibitory factors released by Descemet’s membrane prevent proliferation of endothelial cells has focused some current corneal research on reversal or prevention of this inhibition with exogenous growth factors. The sclera is an opaque layer that consists predominantly of dense connective tissue.


Histology_Ross

Histology_Ross. The sclera is an opaque layer that consists predominantly of dense connective tissue. The sclera is a thick fibrous layer containing flat collagen bundles that pass in various directions and in planes parallel to its surface. Both the collagen bundles and fibrils that form them are irregular in diameter and arrangement. Interspersed between the collagen bundles are fine networks of elastic fibers and a moderate amount of ground substance. Fibroblasts are scattered among these fibers (Plate 107, page 926).


Histology_Ross

Histology_Ross. The opacity of the sclera, like that of other dense connective tissues, is primarily attributable to the irregularity of its structure. The sclera is pierced by blood vessels, nerves, and the optic nerve (see Fig. 24.2). It is 1 mm thick posteriorly, 0.3 to 0.4 mm thick at its equator, and 0.7 mm thick at the corneoscleral margin or “limbus.” The sclera is divided into three rather ill-defined layers:  The episcleral layer (episclera), the external layer, is the loose connective tissue adjacent to the periorbital fat.  The substantia propria (sclera proper, also called Tenon’s capsule), is the investing fascia of the eye and is composed of a dense network of thick collagen fibers.  The suprachoroid lamina (lamina fusca), the inner aspect of the sclera, is located adjacent to the choroid and contains thinner collagen fibers and elastic fibers as well as fibroblasts, melanocytes, macrophages, and other connective tissue cells.


Histology_Ross

Histology_Ross. In addition, the episcleral space (Tenon’s space) is located between the episcleral layer and substantia propria of the sclera. This space and the surrounding periorbital fat allow the eye to rotate freely within the orbit. The tendons of the extraocular muscles attach to the substantia propria of the sclera. The corneoscleral limbus is the transitional zone between the cornea and sclera. At the junction of the cornea and sclera (Fig. 24.6 and Plate 107, page 926), Bowman’s membrane ends abruptly. The overlying epithelium at this site thickens from the 5 cell layers of the cornea to the 10 to 12 cell layers of the conjunctiva. The surface of the limbus is composed of two distinct types of epithelial cells: one type constitutes the conjunctival cells and the other corneal epithelial cells.


Histology_Ross

Histology_Ross. At this junction, the corneal lamellae become less regular as they merge with the oblique bundles of collagen fibers of the sclera. An abrupt transition from the avascular cornea to the well-vascularized sclera also occurs here.


Histology_Ross

Histology_Ross. The limbus region, specifically, the iridocorneal angle, contains the apparatus for the outflow of aqueous humor (Fig. 24.7). In the stromal layer, endothelium-lined channels called the trabecular meshwork (or spaces of Fontana) merge to form the scleral venous sinus (canal of Schlemm). This sinus encircles the eye (see Figs. 24.6 and 24.7). The aqueous humor is produced by the ciliary processes that border the lens in the posterior chamber of the eye. The fluid passes from the posterior chamber into the anterior chamber through the valvelike potential opening between the iris and lens. The fluid then passes through the openings in the trabecular meshwork in the limbus region as it continues its course to enter the scleral venous sinus. Collecting vessels in the sclera, called aqueous veins because they convey aqueous humor instead of blood, transport the aqueous humor to (blood) veins located in the sclera. Changes in the iridocorneal angle may lead to blockage in the drainage of


Histology_Ross

Histology_Ross. veins because they convey aqueous humor instead of blood, transport the aqueous humor to (blood) veins located in the sclera. Changes in the iridocorneal angle may lead to blockage in the drainage of aqueous humor causing glaucoma (see Folder 24.1). The iridocorneal angle can be visualized during eye examination using a gonioscope, a specialized optical device that utilizes mirrors or prisms to refect the light from the iridocorneal angle into the direction of the observer. In conjunction with a slit lamp or operating microscope, the ophthalmologist can examine this region to monitor various eye conditions associated with glaucoma.


Histology_Ross

Histology_Ross. The iris, the most anterior part of the vascular coat, forms a contractile diaphragm in front of the lens. The iris arises from the anterior border of the ciliary body (Fig. 24.7) and is attached to the sclera about 2 mm posterior to the corneoscleral junction. The pupil is the central aperture of this thin disc. The iris is pushed slightly forward as it changes in size in response to light intensity. It consists of highly vascularized connective tissue stroma that is covered on its posterior surface by highly pigmented cells, the posterior pigment epithelium (Fig. 24.8). The basal lamina of sphincter m. pigment layer iris dilator m. canal of Schlemm ciliary muscle ciliary process zonular fibers


Histology_Ross

Histology_Ross. FIGURE 24.6 • Schematic diagram of the structure of the eye. This drawing shows a horizontal section of the eyeball with color-coded layers of its wall. Upper inset. Enlargement of the anterior and posterior chambers is shown in more detail. Note the location of the iridocorneal angle and canal of Schlemm (scleral venous sinus), which drains the aqueous humor from the anterior chamber of the eye. Lower inset. Typical organization of the cells and nerve fibers of the fovea.


Histology_Ross

Histology_Ross. these cells faces the posterior chamber of the eye. The degree of pigmentation is so great that neither the nucleus nor character of the cytoplasm can be seen in the light microscope. Located beneath this layer is a layer of myoepithelial cells, the anterior pigment myoepithelium. The apical (posterior) portions of these myoepithelial cells are laden with melanin granules, which effectively obscure their boundaries with the adjacent posterior pigment epithelial cells. The basal (anterior) portions of myoepithelial cells possess processes containing contractile elements that extend radially and collectively make up the dilator pupillae muscle of the iris. The contractile processes are enclosed by a basal lamina that separates them from the adjacent stroma. Constriction of the pupil is produced by smooth muscle cells located in the stroma of the iris near the pupillary margin of the iris. These circumferentially oriented cells collectively compose the sphincter pupillae muscle.


Histology_Ross

Histology_Ross. The anterior surface of the iris reveals numerous ridges and grooves that can be seen in clinical examination with the ophthalmoscope. When this surface is examined in the light microscope, it appears as a discontinuous layer of fibroblasts and melanocytes. The number of melanocytes in the stroma is responsible for variation in eye color. The function of these pigment-containing cells in the iris is to absorb light rays. If there are few melanocytes in the stroma, eye color is derived from light refected from the pigment present in the cells of the posterior surface of the iris, giving it a blue appearance. As the amount of pigment present in the stroma increases, the color changes from blue to shades of greenish blue, gray, and, fnally, brown. The sphincter pupillae is innervated by parasympathetic nerves; the dilator pupillae muscle is under sympathetic nerve control.


Histology_Ross

Histology_Ross. The sphincter pupillae is innervated by parasympathetic nerves; the dilator pupillae muscle is under sympathetic nerve control. The size of the pupil is controlled by contraction of the sphincter pupillae and dilator pupillae muscles. The process of adaptation (increasing or decreasing the size of the pupil) ensures that only the appropriate amount of light enters the eye. Two muscles are actively involved in adaptation:  The sphincter pupillae muscle, a circular band of smooth muscle cells (Plate 106, page 924), is innervated by parasympathetic nerves carried in the oculomotor nerve (cranial nerve III) and is responsible for reducing pupillary size in response to bright light. Failure of the


Histology_Ross

Histology_Ross. FIGURE 24.7 • Photomicrograph of the ciliary body and iridocorneal angle. This photomicrograph of the human eye shows the anterior portion of the ciliary body and parts of the iris and sclera. The inner surface of the ciliary body forms radially arranged, ridge-shaped elevations, the ciliary processes, to which the zonula fibers are anchored. The ciliary body contains the ciliary muscle, connective tissue with blood vessels of the vascular coat, and the ciliary epithelium, which is responsible for the production of aqueous humor. Anterior to the ciliary body, between the iris and the cornea, is the iridocorneal angle. The scleral venous sinus (canal of Schlemm) located in close proximity to this angle drains the aqueous humor to regulate intraocular pressure. 120. The inset shows that the ciliary epithelium consists of two layers, the outer pigmented layer and the inner nonpigmented layer. 480.


Histology_Ross

Histology_Ross. pupil to respond when light is shined into the eye— “pupil fxed and dilated”—is an important clinical sign showing lack of nerve or brain function.  The dilator pupillae muscle is a thin sheet of radially oriented contractile processes of pigmented myoepithelial cells constituting the anterior pigment epithelium of the iris. This muscle is innervated by sympathetic nerves from the superior cervical ganglion and is responsible for increasing pupillary size in response to dim light. Just before ophthalmoscopic examination, mydriatic agents such as atropine are given as eye drops to cause dilation of the pupil. Acetylcholine (ACh) is the neurotransmitter of the parasympathetic nervous system (it innervates the sphincter pupillae muscle); the addition of atropine blocks muscarinic acetylcholine receptors, temporally blocking the action of the sphincter muscle and leaving the pupil wide open and unreactive to light originating from ophthalmoscope.


Histology_Ross

Histology_Ross. The ciliary body is the thickened anterior portion of the vascular coat and is located between the iris and choroid. The ciliary body extends about 6 mm from the root of the iris posterolaterally to the ora serrata (see Fig. 24.2). As seen from behind, the lateral edge of the ora serrata bears 17 to 34 grooves or crenulations. These grooves mark the anterior limit of both the retina and the choroid. The anterior third of the ciliary body has about 75 radial ridges or ciliary processes (see Fig. 24.7). The fibers of the zonule arise from the grooves between the ciliary processes. The layers of the ciliary body are similar to those of the iris and consist of a stroma and an epithelium. The stroma is divided into two layers:  An outer layer of smooth muscle, the ciliary muscle, makes up the bulk of the ciliary body.  An inner vascular region extends into the ciliary processes.


Histology_Ross

Histology_Ross. The epithelial layer covering the internal surface of the ciliary body is a direct continuation of the two layers of the retinal epithelium (see Fig. 24.1). The ciliary muscle is organized into three functional portions or groups of smooth muscle fibers. The smooth muscle of the ciliary body has its origin in the scleral spur, a ridgelike projection on the inner surface of the sclera at the corneoscleral junction. The muscle fibers spread out in several directions and are classified into three functional groups on the basis of their direction and insertion:


Histology_Ross

Histology_Ross. Glaucoma is a clinical condition resulting from increased intraocular pressure over a sustained period of time. It can be caused by excessive secretion of aqueous humor or impedance of the drainage of aqueous humor from the an-terior chamber. The internal tissues of the eye, particularly the retina, are nourished by the diffusion of oxygen and nutrients from the intraocular vessels. Blood flows normally through these vessels (including the capillaries and veins) when the hydrostatic pressure within the vessels exceeds the intraocular pressure. If the drainage of the aqueous humor is impeded, the intraocular pressure increases be-cause the layers of the eye do not allow the wall to expand. This increased pressure interferes with normal retinal nour-ishment and function, causing the retinal nerve fiber layer to atrophy (Fig. F24.1.1). There are two major types of glaucoma:  Open-angle glaucoma is the most common type of glaucoma and the leading cause of blindness among adults. The


Histology_Ross

Histology_Ross. nerve fiber layer to atrophy (Fig. F24.1.1). There are two major types of glaucoma:  Open-angle glaucoma is the most common type of glaucoma and the leading cause of blindness among adults. The removal of aqueous humor is obstructed be-cause of reduced flow through the trabecular meshwork of the iridocorneal angle into the scleral venous sinus (canal of Schlemm).  Close-angle glaucoma (acute glaucoma) is much less common and is characterized by a narrowed irido-corneal angle that obstructs inflow of the aqueous humor into the scleral venous sinus. Usually it is associ-ated with a sudden, painful, complete blockage of the scleral venous sinus and can result in permanent blind-ness if not treated promptly. Visual deficits associated with glaucoma include blurring of vision and impaired dark adaptation (symptoms that indicate loss of normal retinal function) and halos around lights (a symptom indicating corneal endothelial damage). If the con-dition is not treated, the retina will be


Histology_Ross

Histology_Ross. adaptation (symptoms that indicate loss of normal retinal function) and halos around lights (a symptom indicating corneal endothelial damage). If the con-dition is not treated, the retina will be permanently damaged, and blindness will occur. Treatments are directed toward lowering the intraocular pressure by decreasing the rate of production of aqueous humor or eliminating the cause of the obstruction of normal drainage. Recently, carbonic anhydrase inhibitors that specifically inhibit carbonic an-hydrase isoenzyme CA-II, which plays an important role in the production of aqueous humor in humans, are used as the pharmacologic treatment of choice. Dorzolamide and brinzolamide are two carbonic anhydrase inhibitors that are currently available as eyedrops to treat glaucoma.


Histology_Ross

Histology_Ross.  FOLDER 24.1 Clinical Correlation: Glaucoma FIGURE F24.1.1 • Glaucoma. This image shows a view of the fundus of the left eye in a patient with advanced glaucoma. As a result of the increased intraocular pressure, retinal nerve fibers undergo atrophy and shrink in size. Note a pale optic disc in the center of the image with a less pronounced rim due to atrophy of nerve fibers. Enlargement of the optic nerve cup (central area of the optic disc) is also visible and a characteristic finding for glaucoma. Compare this image to a normal retina in Fig. 24.14. (Courtesy of Dr. Renzo A. Zaldivar.)  The meridional (or longitudinal) portion consists of the outer muscle fibers that pass posteriorly into the stroma of the choroid. These fibers function chiefly in stretching the choroid. It also may help open the iridocorneal angle and facilitate drainage of the aqueous humor.


Histology_Ross

Histology_Ross.  The radial (or oblique) portion consists of deeper muscle fiber bundles that radiate in a fanlike fashion to insert in the ciliary body. Its contraction causes the lens to flatten and thus focus for distant vision.  The circular (or sphincteric) portion consists of inner muscle fiber bundles oriented in a circular pattern that forms a sphincter. It reduces the tension on the lens, causing the lens to accommodate for near vision. Examination of a histologic preparation does not clearly reveal the arrangement of the muscle fibers. Rather, the organizational grouping is based on microdissection techniques. Ciliary processes are ridgelike extensions of the ciliary body from which zonular fibers emerge and extend to the lens.


Histology_Ross

Histology_Ross. Ciliary processes are ridgelike extensions of the ciliary body from which zonular fibers emerge and extend to the lens. Ciliary processes are thickenings of the inner vascular region of the ciliary body. They are continuous with the vascular layers of the choroid. Scattered macrophages containing melanin pigment granules and elastic fibers are present in these processes (Plate 106, page 924). The processes and the ciliary body are covered by a double layer of columnar epithelial cells, the ciliary epithelium, which was originally


Histology_Ross

Histology_Ross. FIGURE 24.8 • Structure of the iris. a. This schematic diagram shows the layers of the iris. Note that the pigmented epithelial cells are reflected as occurs at the pupillary margin of the iris. The two layers of pigmented epithelial cells are in contact with the dilator pupillae muscle. The incomplete layer of fibroblasts and stromal melanocytes is indicated on the anterior surface of the iris. b. Photomicrograph of the iris showing the histologic features of this structure. The lens, which lies posterior to the iris, is included for orientation. The iris is composed of a connective tissue stroma covered on its posterior surface by the posterior pigment epithelium. The basal lamina (not visible) faces the posterior chamber of the eye. Because of intense pigmentation, the histologic features of these cells are not discernible. Just anterior to these cells is the anterior pigment myoepithelium layer (the dashed line separates the two layers). Note that the posterior portion of the


Histology_Ross

Histology_Ross. of these cells are not discernible. Just anterior to these cells is the anterior pigment myoepithelium layer (the dashed line separates the two layers). Note that the posterior portion of the myoepithelial cells contains melanin, whereas the anterior portion contains contractile elements forming the dilator pupillae muscle of the iris. The sphincter pupillae muscle is evident in the stroma. The color of the iris depends on the number of stromal melanocytes scattered throughout the connective tissue stroma. At the bottom, note the presence of the lens. 570.


Histology_Ross

Histology_Ross. derived from the two layers of the optic cup. The ciliary epithelium has three principal functions:  Secretion of aqueous humor Participation in the blood–aqueous barrier (part of the blood–ocular barrier  Secretion and anchoring of the zonular fbers that form the suspensory ligament of the lens The inner cell layer of the ciliary epithelium has a basal lamina facing the posterior and vitreous chambers. The cells in this layer are nonpigmented. The cell layer that has its basal lamina facing the connective tissue stroma of the ciliary body is heavily pigmented and is directly continuous with the pigmented epithelial layer of the retina. The double-layered ciliary epithelium continues over the iris, where it becomes the posterior pigmented epithelium and anterior pigmented myoepithelium. The zonular fibers extend from the basal lamina of the nonpigmented epithelial cells of the ciliary processes and insert into the lens capsule (the thickened basal lamina of the lens).


Histology_Ross

Histology_Ross. The cells of the nonpigmented layer have all the characteristics of a fluid-transporting epithelium, including complex cell-to-cell junctions with a well-developed zonular occludens, extensive lateral and basal plications, and localization of Na/K-ATPase in the lateral plasma membrane. In addition, they have an elaborate rER and Golgi complex consistent with their role in secreting the zonular fibers. The cells of the pigmented layer have a less developed junctional zone and often exhibit large, irregular lateral intercellular spaces. Both desmosomes and gap junctions hold together the apical surfaces of the two cell layers, creating discontinuous “luminal” spaces called ciliary channels.


Histology_Ross

Histology_Ross. The aqueous humor is similar in ionic composition to plasma but contains less than 0.1% protein (compared with 7% protein in plasma). The aqueous humor passes from the ciliary body toward the lens, and then between the iris and lens, before it reaches the anterior chamber of the eye (see Fig. 24.6). In the anterior chamber of the eye, the aqueous humor passes laterally to the angle formed between the cornea and iris. Here it penetrates the tissues of the limbus as it enters the labyrinthine spaces of trabecular meshwork and finally reaches the canal of Schlemm, which communicates with the veins of the sclera (see Folder 24.1). The choroid is the portion of the vascular coat that lies deep to the retina. The choroid is a dark brown vascular sheet only 0.25 mm thick posteriorly and 0.1 mm thick anteriorly. It lies between the sclera and retina (see Fig. 24.1).


Histology_Ross

Histology_Ross. The choroid is a dark brown vascular sheet only 0.25 mm thick posteriorly and 0.1 mm thick anteriorly. It lies between the sclera and retina (see Fig. 24.1). Two layers can be identified in the choroid:  The choriocapillary layer, an inner vascular layer  Bruch’s membrane, a thin, amorphous hyaline membrane


Histology_Ross

Histology_Ross. The choroid is attached firmly to the sclera at the margin of the optic nerve. A potential space, the perichoroidal space (between the sclera and retina), is traversed by thin, ribbon-like, branching lamellae or strands that pass from the sclera to the choroid. These lamellae originate from the suprachoroid lamina (lamina fusca) and consist of large, flat melanocytes scattered between connective tissue elements including collagen and elastic fibers, fibroblasts, macrophages, lymphocytes, plasma cells, and mast cells. The lamellae pass inward to surround the vessels in the remainder of the choroid layer. Free smooth muscle cells, not associated with blood vessels, are present in this tissue. Lymphatic channels called epichoroid lymph spaces, long and short posterior ciliary vessels, and nerves on their way to the front of the eye are also present in the suprachoroid lamina.


Histology_Ross

Histology_Ross. Most of the blood vessels decrease in size as they approach the retina. The largest vessels continue forward beyond the ora serrata into the ciliary body. These vessels can be seen with an ophthalmoscope. The large vessels are mostly veins that course in whorls before passing obliquely through the sclera as vortex veins. The inner layer of vessels, arranged in a single plane, is called the choriocapillary layer. The vessels of this layer provide nutrients to the cells of the retina. The fenestrated capillaries have lumina that are large and irregular in shape. In the region of the fovea, the choriocapillary layer is thicker, and the capillary network is denser. This layer ends at the ora serrata.


Histology_Ross

Histology_Ross. Bruch’s membrane measures 1 to 4 m in thickness and lies between the choriocapillary layer and the pigment epithelium of the retina. It runs from the optic nerve to the ora serrata, where it undergoes modifications before continuing into the ciliary body. Bruch’s membrane is a thin, amorphous refractile layer, also called the lamina vitrea. The transmission electron microscope (TEM) reveals its structure as consisting of a multilaminar sheet containing a center layer of elastic and collagen fibers. Five different layers are identified in Bruch’s membrane:  The basal lamina of the endothelial cells of the choriocap illary layer  A layer of collagen fibers approximately 0.5 m thick  A layer of elastic fibers approximately 2 m thick  A second layer of collagen fibers (thus forming a “sandwich” around the intervening elastic tissue layer)  The basal lamina of the retinal epithelial cells


Histology_Ross

Histology_Ross. At the ora serrata, the collagenous and elastic layers disappear into the ciliary stroma, and Bruch’s membrane becomes continuous with the basal lamina of the RPE of the ciliary body. The retina represents the innermost layer of the eye. The retina, derived from the inner and outer layers of the optic cup, is the innermost of the three concentric layers of the eye (see Fig. 24.1c). It consists of two basic layers:  The neural retina or retina proper is the inner layer that contains the photoreceptor cells.  The RPE is the outer layer that rests on and is firmly attached through the Bruch’s membrane to the choriocapillary layer of the choroid. A potential space exists between the two layers of the retina. The two layers may be separated mechanically in the preparation of histologic specimens. Separation of the layers, “retinal detachment” (Folder 24.2), also occurs in the living state because of eye disease or trauma.


Histology_Ross

Histology_Ross. In the neural retina, two regions or portions that differ in function are recognized:  The nonphotosensitive region (nonvisual part), located anterior to the ora serrata, lines the inner aspect of the ciliary body and the posterior surface of the iris (this portion of the retina is described in the sections on the iris and ciliary body).  The photosensitive region (optic part) lines the inner surface of the eye posterior to the ora serrata except where it is pierced by the optic nerve (see Fig. 24.1).


Histology_Ross

Histology_Ross.  The photosensitive region (optic part) lines the inner surface of the eye posterior to the ora serrata except where it is pierced by the optic nerve (see Fig. 24.1). The site where the optic nerve joins the retina is called the optic disc or optic papilla. Because the optic disc is devoid of photoreceptor cells, it is a blind spot in the visual field. The fovea centralis is a shallow depression located about 2.5 mm lateral to the optic disc. It is the area of greatest visual acuity. The visual axis of the eye passes through the fovea. A yellow-pigmented zone called the macula lutea surrounds the fovea. In relative terms, the fovea is the region of the retina that contains the highest concentration and most precisely ordered arrangement of the visual elements. Layers of the Retina Ten layers of cells and their processes constitute the retina.


Histology_Ross

Histology_Ross. Layers of the Retina Ten layers of cells and their processes constitute the retina. Before discussing the ten layers of the retina, it is important to identify the types of cells found there. This identification will aid in understanding the functional relationships of the cells. Studies of the retina in primates have identified at least 15 types of neurons that form at least 38 different types of synapses. For convenience, neurons and supporting cells can be classified into four groups of cells (Fig. 24.9):  Photoreceptor cells—the retinal rods and cones  Conducting neurons—bipolar neurons and ganglion cells  Association neurons and others—horizontal, centrifugal, interplexiform, and amacrine neurons  Supporting (neuroglial) cells—Mler’s cells, microglial cells, and astrocytes


Histology_Ross

Histology_Ross. The specific arrangement and associations of the nuclei and processes of these cells result in the retina being organized in ten layers that are seen with the light microscope. The ten layers of the retina, from outside inward, are (Figs. 24.9 and 24.10). 1. Retinal pigment epithelium (RPE)—the outer layer of the retina, actually not part of the neural retina but intimately associated with it 2. Layer of rods and cones—contains the outer and inner segments of photoreceptor cells


Histology_Ross

Histology_Ross. A potential space exists in the retina as a vestige of the space between the apical surfaces of the two epithelial lay-ers of the optic cup. If this space expands, the neural retina separates from the retinal pigment epithelium (RPE), which remains attached to the choroid layer. This condition is called retinal detachment. As a result of retinal detach-ment, the photoreceptor cells are no longer supplied by nu-trients from the underlying vessels in the choriocapillary plexus of the choroid. Clinical symptoms of retinal detachment include visual sensations commonly described as a “shower of pepper” or floaters. These are caused by red blood cells extravasated from the capillary vessels that have been injured during the retinal tear or detachment. In addition, some individuals describe sudden flashes of light, as well as a “web” or “veil” in front of the eye in conjunction with the onset of floaters. A detached retina can be observed and diagnosed during ophthalmoscopic eye examination


Histology_Ross

Histology_Ross. flashes of light, as well as a “web” or “veil” in front of the eye in conjunction with the onset of floaters. A detached retina can be observed and diagnosed during ophthalmoscopic eye examination (Fig. F24.2.1). If not repositioned quickly, the detached area of the retina will undergo necrosis, resulting in blindness. More commonly, as the vitreous body ages (in the sixth and sev-enth decades of life), it tends to shrink and pull away from the neural retina, which causes single or multiple tears in the neural retina. An argon laser is often used to repair reti-nal detachment by photocoagulating the edges of the de-tachment and producing scar tissue. This method prevents the retina from further detachment and facilitates the repo-sitioning of photoreceptor cells.


Histology_Ross

Histology_Ross.  FOLDER 24.2 Clinical Correlation: Retinal Detachment fovea area ofretinalarea of detachmentretinal detachment optic disc FIGURE F24.2.1 • Retinal detachment. This image shows a view of the fundus of the right eye in a patient with retinal detachment. The central retinal vessels emerging from the optic disc are in focus, but in the area of the retinal detachment they appear to be out of focus. This is due to the fact that the area of retinal detachment is elevated (note multiple ridges and shadows) and is located anterior to the plane of focus of the ophtalmoscope. (Courtesy of Dr. Renzo A. Zaldivar.) 3. Outer limiting membrane—the apical boundary of Mler’s cells 4. Outer nuclear layer—contains the cell bodies (nuclei) of retinal rods and cones 5. Outer plexiform layer—contains the processes of retinal rods and cones and processes of the horizontal, amacrine, and bipolar cells that connect to them 6.


Histology_Ross

Histology_Ross. Outer plexiform layer—contains the processes of retinal rods and cones and processes of the horizontal, amacrine, and bipolar cells that connect to them 6. Inner nuclear layer—contains the cell bodies (nuclei) of horizontal, amacrine, bipolar, and Mler’s cells 7. Inner plexiform layer—contains the processes of horizontal, amacrine, bipolar, and ganglion cells that connect to each other 8. Ganglion cell layer—contains the cell bodies (nuclei) of ganglion cells 9. Layer of optic nerve fbers—contains processes of ganglion cells that lead from the retina to the brain 10. Inner limiting membrane—composed of the basal lamina of Mler’s cells Each of the layers is more fully described in the following sections (see corresponding numbers). The cells of the RPE (layer 1) have extensions that surround the processes of the rods and cones.


Histology_Ross

Histology_Ross. Each of the layers is more fully described in the following sections (see corresponding numbers). The cells of the RPE (layer 1) have extensions that surround the processes of the rods and cones. The RPE is a single layer of cuboidal cells about 14 m wide and 10 to 14 m tall. The cells rest on Bruch’s membrane of the choroid layer. The pigment cells are tallest in the fovea and adjacent regions, which accounts for the darker color of this region. Adjacent RPE cells are connected by a junctional complex consisting of gap junctions and elaborate zonulae occludentes and adherentes. This junctional complex is the site of the blood–retina barrier.


Histology_Ross

Histology_Ross. The pigment cells have cylindrical sheaths on their apical surface that are associated with, but do not directly contact, the tip of the photoreceptor processes of the adjacent rod and cone cells. Complex cytoplasmic processes project for a short distance between the photoreceptor cells of the rods and cones. Numerous elongated melanin granules, unlike those found elsewhere in the eye, are present in many of these processes. They aggregate on the side of the cell nearest the rods and cones and are the most prominent feature of the cells. The nucleus with its many convoluted infoldings is located near the basal plasma membrane adjacent to Bruch’s membrane. The cells also contain material phagocytosed from the processes of the photoreceptor cells in the form of lamellar debris contained in residual bodies or phagosomes. A supranuclear Golgi apparatus and an extensive network of smooth-surfaced  FOLDER 24.3 Clinical Correlation: Age-Related Macular Degeneration (ARMD)


Histology_Ross

Histology_Ross. Age-related macular degeneration (ARMD) is the most common cause of blindness in older individuals. Al-though the cause of this disease is still unknown, evi-dence suggests both genetic and environmental (UV irradiation, drugs) components. The disease causes loss of central vision, although peripheral vision remains unaffected. Two forms of ARMD are recognized: a dry (at-rophic, nonexudative) form and a wet (exudative, neovas-cular) form. The latter is considered a complication of the first. Dry ARMD is the most common form (90% of all cases) and involves degenerative lesions localized in the area of the macula lutea. The degenerative lesions in-clude a focal thickening of Bruch’s membrane called drusen, atrophy, and depigmentation of RPE, and obliter-ation of capillaries in the underlying choroid layer. These changes lead to deterioration of the overlying photosensi-tive retina, resulting in the formation of blind spots in the visual field (Fig. F24.3.1). Wet ARMD is a complication


Histology_Ross

Histology_Ross. choroid layer. These changes lead to deterioration of the overlying photosensi-tive retina, resulting in the formation of blind spots in the visual field (Fig. F24.3.1). Wet ARMD is a complication of dry ARMD caused by neovascularization of blind spots of the retina in the large drusen. These newly formed, thin, fragile vessels frequently leak and produce exudates and hemorrhages in the space just beneath the retina, result-ing in fibrosis and scarring. These changes are responsi-ble for the progressive loss of central vision over a short time. The treatment of wet ARMD includes conventional laser treatment therapy; however, new surgical methods such as macular translocation have been recently introduced. In this procedure, the retina is detached, translocated, and reattached in a new location, away from the choroid neovascular tissue. Conventional laser treat-ment is then applied to destroy pathologic vessels with-out destroying central vision. FIGURE F24.3.1 • Photograph depicting


Histology_Ross

Histology_Ross. away from the choroid neovascular tissue. Conventional laser treat-ment is then applied to destroy pathologic vessels with-out destroying central vision. FIGURE F24.3.1 • Photograph depicting the visual feld in individuals with age-related macular degeneration. Note that central vision is absent because of the changes in the macula region of the retina. To maximize their remaining vision, individuals with this condition are instructed to use eccentric fixation of their eyes.


Histology_Ross

Histology_Ross. endoplasmic reticulum (sER) surround the melanin granules and residual bodies that are present in the cytoplasm. The RPE serves several important functions, including the following:  It absorbs light passing through the neural retina to prevent reflection and resultant glare.  It isolates the retinal cells from blood-borne substances. It serves as a major component of the blood–retina barrier via tight junctions between RPE cells.  It participates in restoring photosensitivity to visual pigments that were dissociated in response to light. The metabolic apparatus for visual pigment resynthesis is present in the RPE cells.  It phagocytoses and disposes of membranous discs from the rods and cones of the retinal photoreceptor cells. The rods and cones of the photoreceptor cell (layer 2) extend from the outer layer of the neural retina to the pigment epithelium.


Histology_Ross

Histology_Ross. The rods and cones of the photoreceptor cell (layer 2) extend from the outer layer of the neural retina to the pigment epithelium. The rods and cones are the outer segments of photoreceptor cells whose nuclei form the outer nuclear layer of the retina (Figs. 24.10 and 24.11). The light that reaches the photoreceptor cells must first pass through all of the internal layers of the neural retina. The rods and cones are arranged in a palisade manner; therefore, in the light microscope, they appear as vertical striations. The retina contains approximately 120 million rods and 7 million cones. The rods are about 2 m thick and 50 m long (ranging from about 60 m at the fovea to 40 m peripherally). The cones vary in length from 85 m at the fovea to 25 m at the periphery of the retina.