Histology_Ross

Histology_Ross. Functionally, the rods are more sensitive to light and are the receptors used during periods of low light intensity (e.g., at dusk or at night). The rod pigments have a maximum absorption at 496 nm of visual spectrum, and the image provided is one composed of gray tones (a “black and white picture”). In contrast, the cones exist in three classes: L, M, and S (long-, middle-, and short-wavelength sensitive, respectively) that cannot be distinguished morphologically. They are less sensitive to low light but more sensitive to red, green, and blue regions of the visual spectrum. Each class of cones contains a different visual pigment molecule that is activated by the absorption of light at the blue (420 nm), green (531 nm), and red (588 nm) ranges in the color spectrum. Cones provide a visual image composed of color by mixing the appropriate proportion of red, green, and blue light. segment of cones outer membrane outer segment of cones and rods


Histology_Ross

Histology_Ross. segment of cones outer membrane outer segment of cones and rods FIGURE 24.9 • Schematic drawing of the layers of the retina. The interrelationship of the neurons is indicated. Light enters the retina and passes through the inner layers of the retina before reaching the photoreceptor cells of the rods and cones that are closely associated with the pigment epithelium.


Histology_Ross

Histology_Ross. The specificity of the cones provides a functional basis to explain color blindness. Trichromats, almost 90% of the population, are those people who can mix a given color from impulses generated in all three classes of cones. True color-blind individuals (almost all are male) are dichromats and are believed to have a defect in the red-, green-, or (much less commonly) blue-sensitive cones. They are able to distinguish different colors by matching the impulses generated by any of the two normal classes of cones. In addition, about 6% of the population of trichromats matches colors with an unusual proportion of red and green. These individuals are called anomalous trichromats. Each rod and cone photoreceptor consists of three parts:  The outer segment of the photoreceptor is roughly cylindrical or conical (hence, the descriptive name rod or cone). This portion of the photoreceptor is intimately related to microvilli projecting from the adjacent pigment epithelial cells.


Histology_Ross

Histology_Ross.  The connecting stalk contains a cilium composed of nine peripheral microtubule doublets extending from a basal body. The connecting stalk appears as the constricted region of the cell that joins the inner to the outer segment. In this layer of FIGURE 24.10 • Photomicrograph of a human retina. On the basis of histologic features that are evident in this micrograph, the retina can be divided into ten layers as indicated on this photomicrograph. Note that Bruch’s membrane (lamina vitrea) separates the inner layer of the vascular coat (choroid) from the pigment epithelium. 440. region, a thin, tapering process called the calyceal process extends from the distal end of the inner segment to surround the proximal portion of the outer segment (see Fig. 24.11).


Histology_Ross

Histology_Ross. region, a thin, tapering process called the calyceal process extends from the distal end of the inner segment to surround the proximal portion of the outer segment (see Fig. 24.11).  The inner segment is divided into an outer ellipsoid and an inner myoid portion. This segment contains a typical complement of organelles associated with a cell that actively synthesize proteins. A prominent Golgi apparatus, rER, and free ribosomes are concentrated in the myoid region. Mitochondria are most numerous in the ellipsoid region. Micro-tubules are distributed throughout the inner segment. In the outer ellipsoid portion, cross-striated fibrous rootlets may extend from the basal body among the mitochondria.


Histology_Ross

Histology_Ross. The outer segment is the site of photosensitivity, and the inner segment contains the metabolic machinery that supports the activity of the photoreceptor cells. The outer segment is considered a highly modified cilium because it is joined to the inner segment by a short connecting stalk containing a basal body (Fig. 24.12a). With the TEM, 600 to 1,000 regularly spaced horizontal discs are seen in the outer segment (Fig. 24.12). In rods, these FIGURE 24.11 • Schematic diagram of the ultrastructure of rod and cone cells. The outer segments of the rods and cones are closely associated with the adjacent pigment epithelium.


Histology_Ross

Histology_Ross. FIGURE 24.11 • Schematic diagram of the ultrastructure of rod and cone cells. The outer segments of the rods and cones are closely associated with the adjacent pigment epithelium. discs are membrane-bounded structures measuring about 2 m in diameter. They are enclosed within the plasma membrane of the outer segment (Fig. 24.12a). The parallel membranes of the discs are about 6 nm thick and are continuous at their ends. The central enclosed space is about 8 nm across. In both rods and cones, the membranous discs are formed from repetitive transverse infolding of the plasma membrane in the region of the outer segment near the cilium. Autoradiographic studies have demonstrated that rods form new discs by infolding of the plasma membrane throughout their life span. Discs are formed in cones in a similar manner but are not replaced on a regular basis.


Histology_Ross

Histology_Ross. Rod discs lose their continuity with the plasma membrane from which they are derived soon after they are formed. They then pass like a stack of plates, proximally to distally, along the length of the cylindrical portion of the outer segment until they are eventually shed and phagocytosed by the pigment epithelial cells. Thus, each rod disc is a membrane-enclosed compartment within the cytoplasm. Discs within the cones retain their continuity with the plasma membrane (Fig. 24.12b). Rod cells contain the visual pigment rhodopsin; cone cells contain the visual pigment iodopsin.


Histology_Ross

Histology_Ross. Rod cells contain the visual pigment rhodopsin; cone cells contain the visual pigment iodopsin. Rhodopsin (also called visual purple) in rod cells initiates the visual stimulus when it is bleached by light. Rhodopsin is present in globular form on the outer surface of the lipid bilayer (on the cytoplasmic side) of the membranous discs. In the cone cells, the visual pigment on the membranous discs is the photopigment iodopsin. Each cone cell is specialized to respond maximally to one of three colors: red, green, or blue. Both rhodopsin and iodopsin contain a membrane-bound subunit called an opsin and a second component called a chromophore. The opsin of rods is scotopsin; the opsins of cones are photopsins. The chromophore of rods is a vitamin A–derived carotenoid called retinal. Thus, an adequate intake of vitamin A is essential for normal vision. Prolonged dietary defciency of vitamin A leads to the inability to see in dim light (night blindness).


Histology_Ross

Histology_Ross. The interior of the discs of cones is continuous with the extracellular space. The basic difference in the structure of the rod and cone discs—that is, continuity with the plasma membrane—is correlated with the slightly different means by which the visual pigments are renewed in rods and cones. Newly synthesized rhodopsin is incorporated into the membrane of the rod disc as the disc is being formed at the base of the outer segment. It then takes several days for the disc to reach the tip of the outer segment. In contrast, although visual proteins are constantly produced in retinal cones, the proteins are incorporated into cone discs located anywhere in the outer segment. Vision is a process by which light striking the retina is converted into electrical impulses that are transmitted to the brain.


Histology_Ross

Histology_Ross. Vision is a process by which light striking the retina is converted into electrical impulses that are transmitted to the brain. The impulses produced by light reaching the photoreceptor cells are conveyed to the brain by an elaborate network of nerves. The conversion of the incident light into nerve impulses is called visual processing and involves two basic steps:  Step 1 is a photochemical reaction that occurs in the outer segment of the rod and cone receptors as absorbed light energy causes conformational changes in the chromophores. The activated opsin molecules interact with a G-protein called transducin. Transducin then activates phosphodiesterase, which breaks down cyclic GMP (cGMP). In the dark, high levels of cGMP in the photoreceptor cells are bound to the cytoplasmic surface of Na channels, causing them to stay open. As a result, photoreceptor cells have a low membrane potential.


Histology_Ross

Histology_Ross.  Step 2 consists of a decrease in the concentration of cGMP within the cytoplasm of the inner segment of the photoreceptor cells. These changes, which are activated by light energy, decrease the Na permeability of the plasma membrane. When fewer cGMP molecules are bound to Na channel proteins, the photoreceptor becomes hyperpolarized, resulting in a decrease of neurotransmitter (glutamate) secretion. This decrease in glutamate secretion is detected by bipolar cells of the retina, which initiate electrical impulses that are conveyed to the brain. In rods, absorbed light energy causes conformational changes in retinal, converting it to retinol. The conversion of retinal to retinol results in its release from scotopsin (a reaction called bleaching). The energy for this process is provided by the mitochondria located in the inner segment. Mler’s cells and pigment epithelial cells


Histology_Ross

Histology_Ross. FIGURE 24.12 • Electron micrographs of portions of the inner and outer segments of cones and rods. a. This electron micrograph shows the junction between the inner and outer segments of the rod cell. The outer segments contain the horizontally flattened discs. The plane of this section passes through the connecting stalk and cilium. A centriole, a cilium and its basal body, and a calyceal process are identified. 32,000. b. Another electron micrograph shows a similar section of a cone cell. The interior of the discs in the outer segment of the cone is continuous with the extracellular space (arrows). 32,000. (Courtesy of Dr. Toichiro Kuwabara.) also participate in the interconversion of retinal and retinol and the reactions necessary for the resynthesis of rhodopsin.


Histology_Ross

Histology_Ross. During normal functioning of the photoreceptor cells, the membranous discs of the outer segment are shed and phagocytosed by the pigment epithelial cells (Fig. 24.13). It is estimated that each of these cells is capable of phagocytosing and disposing of about 7,500 discs per day. The discs are constantly turning over, and the production of new discs must equal the rate of disc shedding. Discs are shed from both rods and cones. In rods, after a period of sleep, a burst of disc shedding occurs as light first enters the eye. The time of disc shedding in cones is more variable. The shedding of discs in cones also enables the receptors to eliminate superfluous membrane. Although not fully understood, the shedding process in cones also alters the size of the discs so that the conical form is maintained as discs are released from the distal end of the cone.


Histology_Ross

Histology_Ross. FIGURE 24.13 • Electron micrograph of the retinal pigment epithelium in association with the outer segments of rods and cones. Retinal pigment epithelial cells (RPE) contain numerous elongated melanin granules that are aggregated in the apical portion of the cell, where the microvilli extend from the surface toward the outer segments of the rod and cone cells. The retinal pigment epithelial cells contain numerous mitochondria and phagosomes. The arrow indicates the location of the junctional complex between two adjacent cells. 20,000. (Courtesy of Dr. Toichiro Kuwabara.) The outer limiting membrane (layer 3) is formed by a row of zonulae adherentes between Mler’s cells.


Histology_Ross

Histology_Ross. The outer limiting membrane (layer 3) is formed by a row of zonulae adherentes between Mler’s cells. The outer limiting membrane is not a true membrane. It is a row of zonulae adherentes that attaches the apical ends of Mler’s cells (i.e., the end that faces the pigment epithelium) to each other and to the rods and cones (see Fig. 24.10). Because Mler’s cells end at the base of the inner segments of the receptors, they mark the location of this layer. Thus, the supporting processes of Mler’s cells, on which the rods and cones rest, are pierced by the inner and outer segments of the photoreceptor cells. This layer is thought to be a metabolic barrier that restricts the passage of large molecules into the inner layers of the retina. The outer nuclear layer (4) contains the nuclei of the retinal rods and cones.


Histology_Ross

Histology_Ross. The outer nuclear layer (4) contains the nuclei of the retinal rods and cones. The region of the rod cytoplasm that contains the nucleus is separated from the inner segment by a tapering process of the cytoplasm. In cones, the nuclei are located close to the outer segments, and no tapering is seen. The cone nuclei stain lightly and are larger and more oval than rod nuclei. Rod nuclei are surrounded by only a thin rim of cytoplasm. In contrast, a relatively thick investment of cytoplasm surrounds the cone nuclei (see Fig. 24.11). The outer plexiform layer (5) is formed by the processes of the photoreceptor cells and neurons.


Histology_Ross

Histology_Ross. The outer plexiform layer is formed by the processes of retinal rods and cones and the processes of horizontal, interplexiform, amacrine, and bipolar cells. The processes allow the electrical coupling of photoreceptor cells to these specialized interneurons via synapses. A thin process extends from the region of the nucleus of each rod or cone to an inner expanded portion with several lateral processes. The expanded portion is called a spherule in a rod and a pedicle in a cone. Normally, many photoreceptor cells converge onto one bipolar cell and form interconnecting neural networks. Cones located in the fovea, however, synapse with a single bipolar cell. The fovea is also unique in that the compactness of the inner neural layers of the retina causes the photoreceptor cells to be oriented obliquely. Horizontal cell dendritic processes synapse with photoreceptor cells throughout the retina and further contribute to the elaborate neuronal connections in this layer.


Histology_Ross

Histology_Ross. The inner nuclear layer (6) consists of the nuclei of horizontal, amacrine, bipolar, interplexiform, and Mler’s cells. Mler’s cells form the scaffolding for the entire retina. Their processes invest the other cells of the retina so completely that they fill most of the extracellular space. The basal and apical ends of Mler’s cells form the inner and outer limiting membranes, respectively. Microvilli extending from their apical border lie between the photoreceptor cells of the rods and cones. Capillaries from the retinal vessels extend only to this layer. The rods and cones carry out their metabolic exchanges with extracellular fluids transported across the blood–retina barrier of the RPE. The four types of conducting cells—bipolar, horizontal, interplexiform, and amacrine—found in this layer have distinct orientations (see Fig. 24.9).


Histology_Ross

Histology_Ross. The four types of conducting cells—bipolar, horizontal, interplexiform, and amacrine—found in this layer have distinct orientations (see Fig. 24.9).  Bipolar cells and their processes extend to both the inner and outer plexiform layer. In the peripheral regions of the retina, the axons of bipolar cells pass to the inner plexiform layer where they synapse with several ganglion cells. Through these connections, the bipolar cells establish communication with multiple cells in each layer except in the fovea, where they may synapse only with a single ganglion cell to provide greater visual acuity in this region.  Horizontal cells and their processes extend to the outer plexiform layer where they intermingle with processes of bipolar cells. The cells have synaptic connections with rod spherules, cone pedicles, and bipolar cells. This electrical coupling of cells is thought to affect the functional threshold between rods and cones and bipolar cells.


Histology_Ross

Histology_Ross.  Amacrine cells processes pass inward, contributing to a complex interconnection of cells. Their processes branch extensively to provide sites of synaptic connections with axonal endings of bipolar cells and dendrites of ganglion cells. Besides bipolar and ganglion cells, the amacrine cells synapse in the inner plexiform layer with interplexiform and other amacrine cells (see Fig. 24.9).  Interplexiform cells and their processes have synapses in both inner and outer plexiform layers. These cells convey impulses from the inner plexiform to the outer plexiform layer. The inner plexiform layer (7) consists of a complex array of intermingled neuronal cell processes.


Histology_Ross

Histology_Ross. The inner plexiform layer (7) consists of a complex array of intermingled neuronal cell processes. The inner plexiform layer consists of synaptic connections between axons of the bipolar neurons and dendrites of ganglion cells. It also contains synapses between intermingling processes of amacrine cells and bipolar neurons, ganglion cells, and interplexiform neurons. The course of these processes is parallel to the inner limiting membrane, thus giving the appearance of horizontal striations to this layer (see Fig. 24.10). The ganglion cell layer (8) consists of the cell bodies of large multipolar neurons.


Histology_Ross

Histology_Ross. The cell bodies of large multipolar nerve cells, measuring as much as 30 m in diameter, constitute the ganglion cell layer. These nerve cells have lightly staining round nuclei with prominent nucleoli and Nissl bodies in their cytoplasm. An axonal process emerges from the rounded cell body, passes into the nerve fiber layer, and then goes into the optic nerve. The dendrites extend from the opposite end of the cell to ramify in the inner plexiform layer. In the peripheral regions of the retina, a single ganglion cell may synapse with a hundred bipolar cells. In marked contrast, in the macular region surrounding the fovea, the bipolar cells are smaller (some authors refer to them as “midget” bipolar cells), and they tend to make one-to-one connections with ganglion cells. Over most of the retina, the ganglion cells are only a single layer of cells. At the macula, however, they are piled as many as eight deep, although they are absent over the fovea itself. Scattered among the ganglion


Histology_Ross

Histology_Ross. retina, the ganglion cells are only a single layer of cells. At the macula, however, they are piled as many as eight deep, although they are absent over the fovea itself. Scattered among the ganglion cells are small neuroglial cells with densely staining nuclei (see Fig. 24.10).


Histology_Ross

Histology_Ross. The layer of optic nerve fibers (9) contains axons of the ganglion cells. The axonal processes of the ganglion cells form a flattened layer running parallel to the retinal surface. This layer increases in depth as the axons converge at the optic disc (Fig. 24.14). The axons are thin, nonmyelinated processes measuring as much as 5 m in diameter (see Fig. 24.10). The retinal vessels, including the superficial capillary network, are primarily located in this layer. The inner limiting membrane (layer 10) consists of a basal lamina separating the retina from the vitreous body. The inner limiting membrane forms the innermost boundary of the retina. It serves as the basal lamina of Mler’s cells (see Fig. 24.10). In younger individuals, refections from the internal limiting membrane produce a retinal sheen that is seen during ophthalmoscopic examination of the eye. Specialized Regions of the Retina


Histology_Ross

Histology_Ross. Specialized Regions of the Retina The fovea (fovea centralis) appears as a small (1.5 mm in diameter), shallow depression located at the posterior pole of the optical axis of the eye. Its central region, known as the foveola, is about 200 m in diameter (see Fig.24.14). Except for the photoreceptor layer, most of the layers of the retina are markedly reduced or absent in this region (see Fig. 24.6). Here the photoreceptor is composed entirely of cones (approximately 4,000) that are longer and more slender and rodlike than they are elsewhere. In this area, the retina is specialized for discrimination of details and color vision. The ratio between cones and ganglion cells is close to 1:1. Retinal vessels are absent in the fovea, allowing light to pass unobstructed into the cone’s outer segment. The adjacent pigment epithelial cells and choriocapillaris are also thickened in this region.


Histology_Ross

Histology_Ross. The macula lutea is the area surrounding the fovea, approximately 5.5 mm in diameter. It is yellowish because of the presence of yellow pigment (xanthophyll). The macula lutea contains approximately 17,000 cones and gains rods at its periphery. Retinal vessels are also absent in this region. Here the retinal cells and their processes, especially the ganglion cells, are heaped up on the sides of the fovea so that light may pass unimpeded to this most sensitive area of the retina. Vessels of the Retina The central retinal artery and central retinal vein, the vessels that can be seen and assessed with an ophthalmoscope, pass through the center of the optic nerve to enter the bulb of the eye at the optic disc (see Fig. 24.2 and page 898,


Histology_Ross

Histology_Ross. FIGURE 24.14 • Normal view of the fundus in ophthalmoscopic examination of the right eye. The site where the axons converge to form the optic nerve is called the optic disc. Because the optic disc is devoid of photoreceptor cells, it is a blind spot in the visual field. From the center of the optic nerve (clinically called the optic cup), central retinal vessels emerge. The artery divides into upper and lower branches, each of which further divides into nasal and temporal branches (note the nasal and temporal directions on the image). Veins have a similar pattern of tributaries. Approximately 17 degrees or 2.5 times optic disc diameters lateral to the disc, the slightly oval-shaped, blood-vessel-free, and pigmented area represents the macula lutea. The fovea centralis, a shallow depression in the center of the macula lutea, is also visible. (Courtesy of Dr. Renzo A. Zaldivar.) the section on the development of the eye). The central retinal artery provides nutrients to the inner


Histology_Ross

Histology_Ross. in the center of the macula lutea, is also visible. (Courtesy of Dr. Renzo A. Zaldivar.) the section on the development of the eye). The central retinal artery provides nutrients to the inner retinal layers. The artery branches immediately into upper and lower branches, each of which divides again into nasal and temporal branches (see Fig. 24.14). Veins undergo a similar pattern of branching. The vessels initially lie between the vitreous body and inner limiting membrane. As the vessels pass laterally, they also move deeper within the inner retinal layers. Branches from these vessels form a capillary plexus that reaches the inner nuclear layer and therefore provides nutrients to the inner retinal layers (layers 6–10; see pages 907–908). Nutrients to the remaining layers (layers 1–5) are provided by diffusion from the vascular choriocapillary layer of the choroid. The branches of the central retinal artery do not anastomose and therefore are classifed as anatomic end arteries.


Histology_Ross

Histology_Ross. are provided by diffusion from the vascular choriocapillary layer of the choroid. The branches of the central retinal artery do not anastomose and therefore are classifed as anatomic end arteries. Evaluation of the retinal vessels and appearance of the optic disc during the ophthalmoscopy not only provides important information on the state of the eye but also provides early clinical signs of a number of conditions, including elevated intracranial pressure, hypertension, glaucoma, and diabetes.


Histology_Ross

Histology_Ross. The lens is a transparent, avascular, biconvex structure. It is suspended between the edges of the ciliary body by the zonular fbers. The pull of the zonular fibers keeps the lens in a flattened condition. Release of tension causes the lens to fatten or accommodate to bend light rays originating close to the eye so that they focus on the retina. The lens has three principal components (Fig. 24.15):  The lens capsule is a thick basal lamina measuring ap proximately 10 m to 20 m produced by the anterior lens cells.  The Subcapsular epithelium is a cuboidal layer of cells present only on the anterior surface of the lens.  The lens fbers are structures derived from subcapsular epithelial cells. The lens capsule, composed primarily of type IV collagen and proteoglycans, is elastic. It is thickest at the equator where the fibers of the zonule attach to it.


Histology_Ross

Histology_Ross. The lens capsule, composed primarily of type IV collagen and proteoglycans, is elastic. It is thickest at the equator where the fibers of the zonule attach to it. Gap junctions connect the cuboidal cells of the subcapsular epithelium. They have few cytoplasmic organelles and stain faintly. The apical region of the cell is directed toward the internal aspect of the lens and the lens fbers, with which they form junctional complexes. The lens increases in size during normal growth and then continues to produce new lens fibers at an ever-decreasing rate throughout life. The new lens fibers develop from the subcapsular epithelial cells located near the equator (see Fig. 24.15). Cells in this region increase in height and then differentiate into lens fibers.


Histology_Ross

Histology_Ross. As the lens fibers develop, they become highly elongated and appear as thin, flattened structures. They lose their nuclei and other organelles as they become filled with proteins called crystallins. Mature lens fibers attain a length of 7 to 10 mm, a width of 8 to 10 m, and a thickness of 2 m. Near the center of the lens, in the nucleus, the fibers are compressed and condensed to such a degree that individual fibers are impossible to recognize. Despite its density and protein content, the lens is normally transparent (see Fig. 24.15). The high density of lens fibers makes it difficult to obtain routine histologic sections of the lens that are free from artifacts. Changes in the lens are associated with aging. With increasing age, the lens gradually loses its elasticity and ability to accommodate. This condition, called presbyopia, usually occurs in the fourth decade of life. It is easily corrected by wearing reading glasses or using a magnifying lens.


Histology_Ross

Histology_Ross. Loss of transparency of the lens or its capsule is also a relatively common condition associated with aging. This condition, called cataract, may be caused by conformational changes or cross-linking of proteins. The development of a cataract may also be related to disease processes, metabolic or hereditary conditions, trauma, or exposure to a deleterious agent (such as ultraviolet radiation). Cataracts that signifcantly impair vision can usually be corrected surgically by removing the lens and replacing it with a plastic lens implanted in the posterior chamber. The vitreous body is the transparent jellylike substance that fills the vitreous chamber in the posterior segment of the eye. The vitreous body is loosely attached to the surrounding structures, including the inner limiting membrane of the


Histology_Ross

Histology_Ross. The vitreous body is loosely attached to the surrounding structures, including the inner limiting membrane of the FIGURE 24.15 • Structure of the lens. a. This schematic drawing of the lens indicates its structural components. Note that the capsule of the lens is formed by the basal lamina of the lens fibers and the subcapsular epithelium located on the anterior surface of the lens. Also note the location of the germinal zone at the equatorial area of the lens. b. This high-magnification photomicrograph of the germinal zone of the lens (near its equator) shows the active process of lens fiber formation from the subcapsular epithelium. Note the thick lens capsule and the underlying layer of nuclei of lens fibers during their differentiation. The mature lens fibers do not possess nuclei. 570.


Histology_Ross

Histology_Ross. retina. The main portion of the vitreous body is a homogeneous gel containing approximately 99% water (the vitreous humor), collagen, glycosaminoglycans (principally hyaluronan), and a small population of cells called hyalocytes. These cells are believed to be responsible for synthesis of collagen fibrils and glycosaminoglycans. Hyalocytes in routine hematoxylin and eosin (H&E) preparation are difficult to visualize. Often, they exhibit a well-developed rER and Golgi apparatus. Fibroblasts and tissue macrophages are sometimes seen in the periphery of the vitreous body. The hyaloid canal (or Cloquet’s canal), which is not always visible, runs through the center of the vitreous body from the optic disc to the posterior lens capsule. It is the remnant of the pathway of the hyaloid artery of the developing eye. Accessory Structures of the Eye The conjunctiva lines the space between the inner surface of the eyelids and the anterior surface of the eye lateral to the cornea.


Histology_Ross

Histology_Ross. Accessory Structures of the Eye The conjunctiva lines the space between the inner surface of the eyelids and the anterior surface of the eye lateral to the cornea. The conjunctiva is a thin, transparent mucous membrane that extends from the corneoscleral limbus located on the peripheral margin of the cornea across the sclera (bulbar conjunctiva) and covers the internal surface of the eyelids (palpebral conjunctiva). It consists of a stratified columnar epithelium containing numerous goblet cells and rests on a lamina propria composed of loose connective tissue. The goblet cell secretion is a component of the tears that bathe the eye. Conjunctivitis, an infammation of the conjunctiva that is commonly called pinkeye, is characterized by redness, irritation, and watering of the eyes. For more clinical information, see Folder 24.4. The primary function of the eyelids is to protect the eye.


Histology_Ross

Histology_Ross. The primary function of the eyelids is to protect the eye. The skin of the eyelids is loose and elastic to accommodate their movement. Within each eyelid is a flexible support, the tarsal plate, consisting of dense fibrous and elastic tissue. Its lower free margin extends to the lid margin, and its superior border serves for the attachment of smooth muscle fibers of the superior tarsal muscle (of Mler). The undersurface of the tarsal plate is covered by the conjunctiva (Fig. 24.16). The orbicularis oculi muscle, a facial expression muscle, forms a thin oval sheet of circularly oriented skeletal muscle fibers overlying the tarsal plate. In addition, the connective tissue of the eyelid contains tendon fibers of the levator palpebrae superioris muscle that open the eyelid (see Fig. 24.16).


Histology_Ross

Histology_Ross. In addition to eccrine sweat glands, which discharge their secretions directly onto the skin, the eyelid contains four other major types of glands (see Fig. 24.16):  The tarsal glands (Meibomian glands), long seba ceous glands embedded in the tarsal plates, appear as ver tical yellow streaks in the tissue deep in the conjunctiva.  FOLDER 24.4 Clinical Correlation: Conjunctivitis


Histology_Ross

Histology_Ross. Conjunctivitis otherwise known as pinkeye, is an inflam-mation of the conjunctiva. It may be localized in either the palpebral conjunctiva or bulbar conjunctiva. Individuals may present with relatively nonspecific symptoms and signs that include redness, irritation, and watery discharge from the eye (Fig. F24.4.1). The symptoms can also mimic a foreign body sensation. Extended use of contact lenses can cause an allergic or bacterial conjunctivitis and may be the first sign of more serious ocular disease (i.e., corneal ulcer). In general, symptoms that last less than 4 weeks are classified as acute conjunctivitis, and those extending for a longer period are referred to as chronic conjunctivitis. Acute conjunctivitis is most commonly caused by bac-teria; a variety of viruses including HIV, varicella-zoster virus (VZV), and herpes simplex virus (HSV); or allergic reac-tions. Bacterial conjunctivitis often shows an opaque puru-lent discharge containing white cells and desquamated


Histology_Ross

Histology_Ross. HIV, varicella-zoster virus (VZV), and herpes simplex virus (HSV); or allergic reac-tions. Bacterial conjunctivitis often shows an opaque puru-lent discharge containing white cells and desquamated epithelial cells. On eye examination, the purulent discharge and conjunctival papillae help to differentiate between bac-terial and viral etiology. Viral conjunctivitis is most common in adults. Clinically, it presents as a diffuse pinkness of the conjunctiva with particularly numerous lymphoid follicles on the palpebral conjunctiva, often accompanied by en-larged preauricular lymph nodes. Viral conjunctivitis is very contagious and usually associated with a recent upper res-piratory infection. Patients need to be advised to avoid touching their eyes, to wash their hands frequently, and to avoid sharing towels and washcloths. Bacterial conjunctivitis is usually treated with antibiotic eye drops or ointments. For viral etiology, no antimicrobials therapy is needed. However, conservative


Histology_Ross

Histology_Ross. avoid sharing towels and washcloths. Bacterial conjunctivitis is usually treated with antibiotic eye drops or ointments. For viral etiology, no antimicrobials therapy is needed. However, conservative management with artificial tears to keep the eye lubricated may relieve symptoms. Although there is no cure for viral conjunctivitis, symp-tomatic relief may be achieved with warm compresses and artificial tears. For the worst cases, topical corticos-teroid drops may be prescribed to reduce the discomfort of inflammation. However, prolonged use of corticos-teroid drops increases the risk of side effects. Antibiotic drops may also be used for treatment of complementary infections. Viral conjunctivitis usually resolves within 3 weeks. However, in worst cases it may take more than a month. FIGURE F24.4.1 • Conjunctivitis. This photograph of the lower part of the eyeball with reflected lower eyelid shows an infected conjunctiva. The enlarged blood vessels of the conjunctiva are responsible


Histology_Ross

Histology_Ross. F24.4.1 • Conjunctivitis. This photograph of the lower part of the eyeball with reflected lower eyelid shows an infected conjunctiva. The enlarged blood vessels of the conjunctiva are responsible for moderate redness of the eye with conjunctival swelling. Frequently moderate, clear (in allergic conjunctivitis) or purulent (in bacterial conjunctivitis) discharge is visible. (Courtesy of Dr. Renzo A. Zaldivar.)


Histology_Ross

Histology_Ross. About 25 tarsal glands are present in the upper eyelid, and 20 are present in the lower eyelid. The sebaceous secretion of the tarsal glands produces an oily layer on the surface of the tear film that retards the evaporation of the normal tear layer. Blockage of the tarsal gland secretion leads to chalazion (tarsal gland lipogranuloma), an inflammation of the tarsal gland. It presents as a painless cyst usually on the upper eyelid that disappears after a few months without any therapeutic intervention.  Sebaceous glands of eyelashes (glands of Zeis) are small, modified sebaceous glands that are connected with and empty their secretion into the follicles of the eyelashes. Bacterial infection of these sebaceous glands causes a stye (also called hordeolum), a painful tenderness and redness of the affected area of the eyelid.  Apocrine glands of eyelashes (glands of Moll) are small sweat glands with unbranched sinuous tubules that begin as a simple spiral.


Histology_Ross

Histology_Ross.  Apocrine glands of eyelashes (glands of Moll) are small sweat glands with unbranched sinuous tubules that begin as a simple spiral.  Accessory lacrimal glands are compound serous tubuloalveolar glands that have distended lumina. They are located on the inner surface of the upper eyelids (glands of Wolfring) and in the fornix of the lacrimal sac (glands of Krause). All glands of the human eyelid are innervated by neurons of the autonomic nervous system, and their secretion is synchronized with the lacrimal glands by a common neurotransmitter, vasoactive intestinal polypeptide (VIP). The eyelashes emerge from the most anterior edge of the lid margin, in front of the openings of the Meibomian glands. The lashes are short, stiff, curved hairs and may occur in double or triple rows. The lashes on the same eyelid margin may have different lengths and diameters. The lacrimal gland produces tears that moisten the cornea and pass to the nasolacrimal duct.


Histology_Ross

Histology_Ross. The lacrimal gland produces tears that moisten the cornea and pass to the nasolacrimal duct. Tears are produced by the lacrimal glands and to a lesser degree by the accessory lacrimal glands. The lacrimal gland is duct of tarsalgland glands apocrine glands of eyelids (of Moll) eyelids (of Moll) eyelash sebaceous glands(of Zeis) of eyelashes (of Zeis) FIGURE 24.16 • Structure of the eyelid. a. This schematic drawing of the eyelid shows the skin, associated skin appendages, muscles, tendons, connective tissue, and conjunctiva. Note the distribution of multiple small glands associated with the eyelid and observe the reflection of the palpebral conjunctiva in the fornix of the lacrimal sac to become the bulbar conjunctiva.


Histology_Ross

Histology_Ross. b. Photomicrograph of a sagittal section of the eyelid stained with picric acid for better visualization of epithelial components of the skin and the numerous glands. In this preparation, muscle tissue (i.e., orbicularis oculi muscle) stains yellow, and the epithelial cells of skin, conjunctiva, and glandular epithelium are green. Note the presence of the numerous glands within the eyelid. The tarsal (Meibomian) gland is the largest gland, and it is located within the dense connective tissue of the tarsal plates. This sebaceous gland secretes into ducts opening onto the eyelids. 20. Inset. Higher magnification of a tarsal gland from the boxed area, showing the typical structure of a holocrine gland. 60.


Histology_Ross

Histology_Ross. located beneath the conjunctiva on the upper lateral side of the orbit (Fig. 24.17). The lacrimal gland consists of several separate lobules of tubuloacinar serous glands. The acini have large lumina lined with columnar cells. Myoepithelial cells, located below the epithelial cells within the basal lamina, aid in the release of tears. Approximately 12 ducts drain from the lacrimal gland into the reflection of conjunctiva just beneath the upper eyelid, known as the fornix of the lacrimal sac.


Histology_Ross

Histology_Ross. Tears drain from the eye through lacrimal puncta, the small openings of the lacrimal canaliculi, located at the medial angle. The upper and lower canaliculi join to form the common canaliculus, which opens into the lacrimal sac. The sac is continuous with the nasolacrimal duct, which opens into the nasal cavity below the inferior turbinate. A pseudostratified ciliated epithelium lines the lacrimal sac and the nasolacrimal duct. Dacryocystitis is an infammation of the lacrimal sac that is frequently caused by an obstruction of the nasolacrimal duct. It can be acute, chronic, or congenital. It usually affects older individuals and is most often secondary to stenosis of the lacrimal canaliculi. Tears protect the corneal epithelium and contain antibacterial and UV-protective agents.


Histology_Ross

Histology_Ross. Tears protect the corneal epithelium and contain antibacterial and UV-protective agents. Tears keep the conjunctiva and corneal epithelium moist and wash foreign material from the eye as they flow across the corneal surface toward the medial angle of the eye (see Fig. 24.17). The thin film of tears covering the corneal surface is not homogeneous but a mixture of products secreted by the lacrimal glands, the accessory lacrimal glands, the goblet cells of the conjunctiva, and the tarsal glands of the eyelid. The tear film contains proteins (tear albumins, lactoferrin), enzymes (lysozyme), lipids, metabolites, electrolytes, and drugs, the latter secreted during therapy. The tear cationic protein lactoferrin increases the activity of various antimicrobial agents such as lysozyme.


Histology_Ross

Histology_Ross. The tear cationic protein lactoferrin increases the activity of various antimicrobial agents such as lysozyme. FIGURE 24.17 • Schematic diagram of the eye and lacrimal apparatus. This drawing shows the location of the lacrimal gland and components of the lacrimal apparatus, which drains the lacrimal fluid into the nasal cavity. The eye is moved within the orbit by coordinated contraction of extraocular muscles.


Histology_Ross

Histology_Ross. The eye is moved within the orbit by coordinated contraction of extraocular muscles. Six muscles of the eyeball (also called extraocular or extrinsic muscles) attach to each eye. These are the medial, lateral, superior, and inferior rectus muscles and the superior and inferior oblique muscles. The superior oblique muscle is innervated by the trochlear nerve (cranial nerve IV). The lateral rectus muscle is innervated by the abducens nerve (cranial nerve VI). All of the remaining extraocular muscles are innervated by the oculomotor nerve (cranial nerve III). The combined, precisely controlled action of these muscles allows vertical, lateral, and rotational movement of the eye. Normally, the actions of the muscles of both eyes are coordinated so that the eyes move in parallel (called conjugate gaze).


Histology_Ross

Histology_Ross. The human eye is a complex sensory organ that provides sight. The wall of the eye consists of three concentric layers or coats: the retina, the inner layer; the uvea, the middle or vascular layer; and the corneosclera, the outer fibrous layer. The eye is often compared to a simple camera with a lens to capture and focus light, a diaphragm to regulate the amount of light, and film to record the image. In the eye, the cornea and lens concentrate and focus light on the retina. The iris, located between the cornea and lens, regulates the size of the pupil through which light enters the eye. Photoreceptor cells (rods and cones) in the retina detect the intensity (rods) and color (cones) of the light that reaches them and encode the various parameters for transmission to the brain via the optic nerve (cranial nerve II). The eye measures 25 mm in diameter. It is suspended in the bony orbit by six extrinsic striated muscles that control its movement. The extraocular muscles are coordinated so


Histology_Ross

Histology_Ross. nerve (cranial nerve II). The eye measures 25 mm in diameter. It is suspended in the bony orbit by six extrinsic striated muscles that control its movement. The extraocular muscles are coordinated so that both eyes move synchronously, with each moving symmetrically around its own central axis. A thick layer of adipose tissue partially surrounds and cushions the eye as it moves within the orbit.


Histology_Ross

Histology_Ross. Modifed drawing of human eye, meridional perspective by E. Sobotta. The innermost layer is the retina (R), which consists of several layers of cells. Among these are receptor cells (rods and cones), neurons (e.g., bipolar and ganglion cells), supporting cells, and a pigment epithelium (see Plate 105). The receptor components of the retina are situated in the posterior three fifths of the eyeball. At the anterior boundary of the receptor layer, the ora serrata (OS), the retina becomes reduced in thickness, and nonreceptor components of the retina continue forward to cover the posterior or inner surface of the ciliary body (CB) and the iris (I). This anterior nonreceptor extension of the inner layer is highly pigmented, and the pigment (melanin) is evident as the black inner border of these structures.


Histology_Ross

Histology_Ross. The uvea, the middle layer of the eyeball, consists of the choroid, the ciliary body, and the iris. The choroid is a vascular layer; it is relatively thin and difficult to distinguish in the accompanying figure except by location. On this basis, the choroid (Ch) is identified as being just external to the pigmented layer of the retina. It is also highly pigmented; the choroidal pigment is evident as a discrete layer in several parts of the section. Anterior to the ora serrata, the uvea is thickened; here, it is called the ciliary body (CB). This contains the ciliary muscle (see Plate 106), which brings about adjustments of the lens to focus light. The ciliary body also contains processes to which the zonular fibers are attached. These fibers function as suspensory ligaments of the lens (L). The iris (I ) is the most anterior component of the uvea and contains a central opening, the pupil.


Histology_Ross

Histology_Ross. The outermost layer of the eyeball, the fbrous layer, consists of the sclera (S) and the cornea (C). Both of these contain collagenous fibers as their main structural element; however, the cornea is transparent, and the sclera is opaque. The extrinsic muscles of the eye insert into the sclera and effect movements of the eyeball. These are not included in the preparation except for two small pieces of a muscle insertion (arrows) in the lower left and top center of the illustration. Posteriorly, the sclera is pierced by the emerging optic nerve (ON ). A deep depression in the neural retina lateral to the optic nerve (above the ON in this figure) is the fovea centralis (FC ), the thinnest and most sensitive portion of the neural retina.


Histology_Ross

Histology_Ross. The lens is considered in Plate 107. Just posterior to the lens is the large cavity of the eye, the vitreous cavity (V ), which is filled with a thick jellylike material, the vitreous humor or body. Anterior to the lens are two additional, fluid-filled chambers of the eye, the anterior chamber (AC ) and the posterior chamber (PC ), separated by the iris. KEY AC, anterior chamber C, cornea CB, ciliary body Ch, choroid FC, fovea centralis I, iris L, lens ON, optic nerve OS, ora serrata PC, posterior chamber R, retina S, sclera V, vitreous cavity arrows, muscle insertions PLATE 105 Eye II: Retina


Histology_Ross

Histology_Ross. The retina and optic nerve are projections of the forebrain. The fibrous cover of the optic nerve is an extension of the meninges of the brain. The neural retina is a multilayered structure consisting of photoreceptors (rods and cones), neurons, some of which are specialized as conducting and associating neurons, and supporting cells (Mler’s cells). External to the neural retina is a layer of simple columnar retinal pigment epithelium (RPE). The Mler’s cells are comparable to neuroglia in the rest of the central nervous system. Processes of Mler’s cells ramify virtually through the entire thickness of the retina. The internal limiting membrane is the basal lamina of these cells; the external limiting membrane is actually a line formed by the junctional complexes between processes of these cells and the photoreceptor cells. The neurons of the retina are arranged sequentially in three layers: (1) a deep layer of rods and cones; (2) an intermediate layer of bipolar, horizontal, and


Histology_Ross

Histology_Ross. these cells and the photoreceptor cells. The neurons of the retina are arranged sequentially in three layers: (1) a deep layer of rods and cones; (2) an intermediate layer of bipolar, horizontal, and amacrine cells; and (3) a superficial layer of ganglion cells. Nerve impulses originating in the rods and cones are transmitted to the intermediate layer and then to the ganglion cells. Synaptic connections occur in the outer plexiform layer (between the rods and cones and the intermediate neuronal layer) and the inner plexiform layer (between the intermediate layer and the ganglion cells), resulting in summation and neuronal integration. Finally, the ganglion cells send their axons to the brain as components of the optic nerve.


Histology_Ross

Histology_Ross. Optic disc and nerve, eye, human, H&E 65. The site where the optic nerve leaves the eyeball is called the optic disc (OD). It is characteristically marked by a depression, evident here. Receptor cells are not present at the optic disc, and because it is not sensitive to light stimulation, it is sometimes referred to as the blind spot. The fibers that give rise to the optic nerve originate in the retina, more specifically, in the ganglion cell layer (see below). They traverse the sclera through a number of openings (arrows) to form the optic nerve (ON ). The region of the sclera that contains these openings is called the lamina cribrosa (LC) or cribriform plate. The optic nerve contains a central artery and vein (not seen here) that also traverse the lamina cribrosa. Branches of these blood vessels (BV ) supply the inner portion of the retina. PLATE 105 • EYE II: RETINA Retina, eye, human, H&E 325.


Histology_Ross

Histology_Ross. PLATE 105 • EYE II: RETINA Retina, eye, human, H&E 325. On the basis of structural features that are evident in histologic sections, the retina is divided into ten layers, from posterior to anterior, as listed below and labeled in this figure: 1. Retinal pigment epithelium (RPE ), the outermost layer of the retina 2. Layer of rods and cones (R&C ), the photoreceptor layer of the retina 3. External limiting membrane (ELM ), a line formed by the junctional complexes of the photoreceptor cells 4. Outer nuclear layer (ONL), containing nuclei of rod and cone cells 5. Outer plexiform layer (OPL), containing neural processes and synapses of rod and cone cells with bipolar, amacrine, interplexiform and horizontal cells 6. Inner nuclear layer (INL), containing nuclei of bipolar, horizontal, interplexiform amacrine, and Mler’s cells 7. Inner plexiform layer (IPL), containing processes and synapses of bipolar, horizontal, interplexiform amacrine, and ganglion cells 8.


Histology_Ross

Histology_Ross. Inner plexiform layer (IPL), containing processes and synapses of bipolar, horizontal, interplexiform amacrine, and ganglion cells 8. Layer of ganglion cells (GC ), containing cell bodies and nuclei of ganglion cells 9. Nerve fiber layer (NFL), containing axons of ganglion cells 10. Internal limiting membrane (ILM ), consisting of the external (basal) lamina of Mler’s cells This figure also shows the innermost layer of the choroid (Ch), a cell-free membrane, the lamina vitrea (LV ), also called Bruch’s membrane. Electron micrographs reveal that it corresponds to the basement membrane of the pigment epithelium. Immediately external to the lamina vitrea is the capillary layer of the choroid (lamina choriocapillaris). These vessels supply the outer part of the retina.


Histology_Ross

Histology_Ross. KEY BV, blood vessels Ch, choroid ELM, external limiting membrane GC, layer of ganglion cells ILM, internal limiting membrane INL, inner nuclear layer (nuclei of bipolar, horizontal, amacrine, and Mler’s cells) IPL, inner plexiform layer LC, lamina cribrosa LV, lamina vitrea NFL, nerve fiber layer OD, optic disc ON, optic nerve ONL, outer nuclear layer (nuclei of rod and cone cells) OPL, outer plexiform layer RPE, retinal pigment epithelium R&C, layer of rods and cones arrows, openings in sclera (lamina cribrosa) PLATE 106 Eye III: Anterior Segment


Histology_Ross

Histology_Ross. PLATE 106 Eye III: Anterior Segment The anterior segment is that part of the eye anterior to the ora serrata, the most anterior extension of the neural retina, and includes the anterior and posterior chambers and the structures that define them. These include the cornea and sclera, the iris, the lens, the ciliary body, and the connections between the basal lamina of the ciliary processes and the lens capsule (thick basal lamina of the lens epithelium) that form the suspensory ligament of the lens, the zonular fbers. The posterior chamber is bounded posteriorly by the anterior surface of the lens and anteriorly by the posterior surface of the iris. The ciliary body forms the lateral boundary. Aqueous humor flows through the pupil into the anterior chamber, which occupies the space between the cornea and the iris, and drains into the canal of Schlemm. Anterior segment, eye, human, H&E 45; inset 75.


Histology_Ross

Histology_Ross. Anterior segment, eye, human, H&E 45; inset 75. A portion of the anterior segment of the eye, shown in this figure, includes parts of the cornea (C ), sclera (S), iris (I ), ciliary body (CB), anterior chamber (AC ), posterior chamber (PC ), lens (L), and zonular fibers (ZF ).


Histology_Ross

Histology_Ross. The relationship of the cornea to the sclera is illustrated to advantage here. The junction between the two (arrows) is marked by a 924 change in staining, with the substance of the cornea appearing lighter than that of the sclera. The corneal epithelium (CEp) is continuous with the conjunctival epithelium (CjEp) that covers the sclera. Note that the epithelium thickens considerably at the corneoscleral junction and resembles that of the oral mucosa. The conjunctival epithelium is separated from the dense fibrous component of the sclera by a loose vascular connective tissue. Together, this connective tissue and the epithelium constitute the conjunctiva (Cj). The epithelial-connective tissue junction of the conjunctiva is irregular; in contrast, the undersurface of the corneal epithelium presents an even profile.


Histology_Ross

Histology_Ross. Just lateral to the junction of the cornea and sclera is the canal of Schlemm (CS; see also figure below). This canal takes a circular route about the perimeter of the cornea. It communicates with the anterior chamber through a loose trabecular meshwork of tissue, the spaces of Fontana. The canal of Schlemm also communicates with episcleral veins. By means of its communications, the canal of Schlemm provides a route for the fluid in the anterior and posterior chambers to reach the bloodstream. The inset shows the tip of the iris. Note the heavy pigmentation on the posterior surface of the iris, which is covered by the same double-layered epithelium as the ciliary body and ciliary processes. In the ciliary epithelium, the outer layer is pigmented and the inner layer is nonpigmented. In the iris, both layers of the iridial epithelium (IEp) are heavily pigmented. A portion of the iridial constrictor muscle (M ) is seen beneath the epithelium. PLATE 106 • EYE III: ANTERIOR SEGMENT


Histology_Ross

Histology_Ross. PLATE 106 • EYE III: ANTERIOR SEGMENT Anterior segment, eye, human, H&E 90; inset 350. Immediately internal to the anterior margin of the sclera (S) is the ciliary body (CB). The inner surface of this forms radially arranged, ridge-shaped elevations, the ciliary processes (CP), to which the zonular fibers (ZF ) are anchored. From the outside in, the components of the ciliary body are the ciliary muscle (CM), the connective tissue (vascular) layer (VL) representing the choroid coat in the ciliary body, the lamina vitrea (LV, inset), and the ciliary epithelium (CiEp, inset). The ciliary epithelium consists of two layers (inset), the pigmented layer (PE ) and the nonpigmented layer (npE ). The lamina vitrea is a continuation of the same layer of the choroid; it is the basement membrane of the pigmented ciliary epithelial cells.


Histology_Ross

Histology_Ross. The ciliary muscle is arranged in three patterns. The outer layer is immediately deep to the sclera. These are the meridionally arranged fibers of Brke. The outermost of these continues more posteriorly into the choroid and is referred to as the tensor muscle of the choroid. The middle layer is the radial group. It radiates from the region of the sclerocorneal junction into the ciliary body. The innermost layer of muscle cells is circularly arranged. These are seen in cross section. The circular artery (CA; barely discernible) and vein (CV) for the iris, also cut in cross section, are just anterior to the circular group of muscle cells.


Histology_Ross

Histology_Ross. KEY A, artery AC, anterior chamber C, cornea CA, circular artery CB, ciliary body CEp, corneal epithelium Ch, choroid CiEp, ciliary epithelium Cj, conjunctiva CjEp, conjunctival epithelium CM, ciliary muscle CP, ciliary processes CS, canal of Schlemm CV, circular vein I, iris IEp, iridial epithelium L, lens LV, lamina vitrea M, iridial constrictor muscle npE, nonpigmented layer of ciliary epithelium PC, posterior chamber PE, pigmented layer of ciliary epithelium S, sclera V, vein VL, vascular layer (of ciliary body) ZF, zonular fibers arrows, junction between cornea and sclera PLATE 107 Eye IV: Sclera, Cornea, and Lens


Histology_Ross

Histology_Ross. The transparent cornea is the primary dioptric (refractive element) of the eye and is covered with nonkeratinized, stratified squamous epithelium. Its stroma consists of alternating lamellae of collagen fibrils and fibroblasts (keratocytes). The fibrils in each lamella are extremely uniform in diameter and uniformly spaced; fibrils in adjacent lamellae are arranged at approximately right angels to each other. This orthogonal array of highly regular fibrils is responsible for the transparency of the cornea. The posterior surface is covered with a single layer of low cuboidal cells, the corneal endothelium, which rest on a thickened basal lamina called Descemet’s membrane. Nearly all of the metabolic exchanges of the avascular cornea occur across the endothelium. Damage to this layer leads to corneal swelling and can produce temporary or permanent loss of transparency. The lens is a transparent, avascular, biconvex epithelial structure suspended by the zonular fibers. Tension on these


Histology_Ross

Histology_Ross. to corneal swelling and can produce temporary or permanent loss of transparency. The lens is a transparent, avascular, biconvex epithelial structure suspended by the zonular fibers. Tension on these fibers keeps the lens flattened; reduced tension allows it to fatten or accommodate to bend light rays originating close to the eye to focus them on the retina.


Histology_Ross

Histology_Ross. PLATE 107 • EYE IV: SCLERA, CORNEA, AND LENS Corneoscleral junction, eye, human, H&E 130. in thickness and rests on a loose vascular connective tissue. Together, this epithelium and underlying connective tissue represents the conjunctiva This low-magnification micrograph shows the full thickness of (Cj). The white opaque appearance of the sclera is due to the irregular dense the sclera just lateral to the corneoscleral junction or limbus. arrangement of the collagen fibers that make up the stroma (S ). The canal To the left of the arrow is sclera; to the right is a small amount of Schlemm (CS ) is seen at the left close to the inner surface of the sclera. of corneal tissue. The conjunctival epithelium (CjEp) is irregular


Histology_Ross

Histology_Ross. of corneal tissue. The conjunctival epithelium (CjEp) is irregular Corneoscleral junction and canal of Schlemm, eye, the sclera. Note that Bowman’s membrane (B), lying under the corneal human, H&E 360. epithelium, is just perceptible but disappears beneath the conjunctival epithelium. Figure below shows at higher magnification the canal of Schlemm Upper figure is a higher-magnification micrograph showing (CS ) than does top left figure. That the space shown here is not an artithe transition from the corneal epithelium (CEp) to the irfact is evidenced by the endothelial lining cells (En) that face the lumen. Cornea, eye, human, H&E 175. white spaces seen here and in figure on left are artifacts). Nuclei (N ) of the keratocytes of the stroma lie between lamellae. The corneal epithelium rests


Histology_Ross

Histology_Ross. Cornea, eye, human, H&E 175. white spaces seen here and in figure on left are artifacts). Nuclei (N ) of the keratocytes of the stroma lie between lamellae. The corneal epithelium rests This low-magnification micrograph shows the full thickness of on a thickened anterior basement membrane called Bowman’s membranethe cornea (C) and can be compared with the sclera shown in (B). The posterior surface of the cornea is lined by a simple squamous figure on left. The corneal epithelium (CEp) presents a uniepithelium called the corneal endothelium (CEn); its thick posterior base-form thickness and the underlying stroma (S ) has a more ment membrane is called Descemet’s membrane (D). homogeneous appearance than the stroma of the sclera (the


Histology_Ross

Histology_Ross. homogeneous appearance than the stroma of the sclera (the Corneal epithelium and endothelium, eye, human, underlying stroma (S ). Note that the stromal tissue has a homogeneous ap-H&E 360. pearance, a reflection of the dense packing of its collagen fibrils. The flattened nuclei belong to the keratocytes. Lower figure shows the posterior Upper is a higher magnification showing the corneal epithe surface of the cornea. Note the thick homogeneous Descemet’s memlium (CEp) with its squamous surface cells, the very thick brane (D) and the underlying corneal endothelium (CEn). homogeneous-appearing Bowman’s membrane (B), and the Lens, eye, human, H&E 360. are present on the anterior surface of the lens, but at the lateral margin they become extremely elongated and form layers that extend toward the center This micrograph shows a portion of the lens near its equator.


Histology_Ross

Histology_Ross. This micrograph shows a portion of the lens near its equator. of the lens. These elongated columns of epithelial cytoplasm are referred to The lens consists entirely of epithelial cells surrounded by a as lens fbers (LF ). New cells are produced at the margin of the lens and homogeneous-appearing lens capsule (LC ) to which the displace the older cells inwardly. Eventually, the older cells lose their nuclei, zonula fibers attach. The lens capsule is a very thick basal lamas evidenced by the deeper portion of the cornea in this micrograph. ina of the epithelial cells. Simple cuboidal lens epithelial cells KEY AC, anterior chamber B, Bowman’s membrane BV, blood vessels C, cornea CEn, corneal endothelium CEp, corneal epithelium Cj, conjunctiva CjEp, conjunctival epithelium CS, canal of Schlemm D, Descemet’s membrane En, endothelial lining cells LC, lens capsule LF, lens fibers N, nuclei S, stroma


Histology_Ross

Histology_Ross. PLATE 107 • EYE IV: SCLERA, CORNEA, AND LENSLFLFCEnCEnDCSCSBCjEpCjEpCEpCEpBCEpCEpCEnCEnDCSNBCEpCEpBVBVCSCSSCjEpCjEpCjCjCjCjEpSBVCSACCEpBSCCEnDACNCjEpCEpBCEpBDCEnEnCSLFLCSSSS OVERVIEW OF THE EAR / 928 EXTERNAL EAR / 928 MIDDLE EAR / 929 INTERNAL EAR / 932 Structures of the Bony Labyrinth / 932 Structures of the Membranous Labyrinth / 933 Sound Perception / 941 Innervation of the Internal Ear / 942 Blood Vessels of the Membranous Labyrinth / 945 Folder 25.1 Clinical Correlation: Otosclerosis / 933 Folder 25.2 Clinical Correlation: Hearing Loss— Vestibular Dysfunction / 934 Folder 25.3 Clinical Correlation: Vertigo / 937


Histology_Ross

Histology_Ross. The ear is a three-chambered sensory organ that functions as an auditory system for sound perception and as a vestibular system for balance. Each of the three divisions of the ear— the external ear, middle ear, and internal ear—is an essential part of the auditory and vestibular systems (Fig. 25.1). The external and middle ear collect and conduct sound energy to the internal ear, where auditory sensory receptors convert that energy into electrical impulses. The sensory receptors of the vestibular system respond to gravity and movement of the head. They are responsible for the sense of balance and equilibrium and help to coordinate movements of the head and eyes. The ear develops from surface ectoderm and components of the first and second pharyngeal arch.


Histology_Ross

Histology_Ross. Embryologically, the functions of the ear—hearing and balance—are elaborated from an invagination of surface ectoderm that appears on each side of the myelencephalon. This invagination forms the otic vesicle (otocyst), which sinks deep to the surface ectoderm into the underlying mesenchyme (Fig. 25.2). The otic vesicle serves as a primordium for development of the epithelia that line the membranous labyrinth of the internal ear. Later, development of the first and part of the second pharyngeal arch provides structures that augment hearing. The endodermal component of the first pouch gives rise to the tubotympanic recess, which ultimately develops into the auditory tube (Eustachian tube) and the middle ear and its epithelial lining. The corresponding ectodermal outgrowth of the first pharyngeal groove gives rise to the external acoustic meatus and its epithelial lining (see Fig. 25.2). The connective tissue part of the pharyngeal arches produces the ossicles. The malleus and incus


Histology_Ross

Histology_Ross. groove gives rise to the external acoustic meatus and its epithelial lining (see Fig. 25.2). The connective tissue part of the pharyngeal arches produces the ossicles. The malleus and incus develop from the first pharyngeal arch, and the stapes from the second pharyngeal arch. The sensory epithelia of the membranous labyrinth that originates from the otic vesicle link with cranial nerve VIII, which is an outgrowth of the central nervous system. The cartilaginous, bony, and muscular structures of the ear develop from the mesenchyme surrounding these early epithelia.


Histology_Ross

Histology_Ross. The auricle is the external component of the ear that collects and amplifies sound. The auricle (pinna) is the oval appendage that projects from the lateral surface of the head. The characteristic shape of the auricle is determined by an internal supporting structure of elastic cartilage. Thin skin with hair follicles, sweat glands, and sebaceous glands cover the auricle. The auricle is considered a nearly vestigial structure in humans, compared with its development and role in other animals. However, it is an essential component in sound localization and amplification. The external acoustic meatus conducts sounds to the tympanic membrane. The external acoustic meatus is an air-filled tubular space that follows a slightly S-shaped course for about 25 mm to the tympanic membrane (eardrum). The wall of the canal


Histology_Ross

Histology_Ross. The external acoustic meatus is an air-filled tubular space that follows a slightly S-shaped course for about 25 mm to the tympanic membrane (eardrum). The wall of the canal FIGURE 25.1 • Three divisions of the ear. The three divisions of the ear are represented by different colors and consist of the external ear (auricle and external acoustic meatus; pink tone), the middle ear (tympanic cavity, auditory ossicles, tympanic membrane, and auditory tube; green), and the internal ear containing the bony labyrinth (semicircular canals, vestibule, and cochlea; blue) and the membranous labyrinth (not visible). is continuous externally with the auricle. The wall of the lateral one third of the canal is cartilaginous and is continuous with the elastic cartilage of the auricle. The medial two thirds of the canal is contained within the temporal bone.


Histology_Ross

Histology_Ross. The lateral part of the canal is lined by skin that contains hair follicles, sebaceous glands, and ceruminous glands but no eccrine sweat glands. The coiled tubular ceruminous glands closely resemble the apocrine glands found in the axillary region. Their secretion mixes with that of the sebaceous glands and desquamated cells to form cerumen, or earwax. The cerumen lubricates the skin and coats the meatal hairs to impede the entry of foreign particles into the ear. Excessive accumulation of cerumen can plug the meatus, however, resulting in conductive hearing loss. The medial part of the canal located within the temporal bone has thinner skin and fewer hairs and glands. The middle ear is an air-filled space that contains three small bones, the ossicles.


Histology_Ross

Histology_Ross. The middle ear is an air-filled space that contains three small bones, the ossicles. The middle ear is located in an air-filled space, called the tympanic cavity, within the temporal bone (Fig. 25.3). It is spanned by three small bones, the auditory ossicles, which are connected by two movable joints. The middle ear also contains the auditory tube (Eustachian tube) as well as the muscles that attach to the ossicles. The middle ear is bounded anteriorly by the auditory tube and posteriorly by the spongy bone of the mastoid process, which contains the mastoid antrum and other, smaller air-filled spaces called mastoid cells. Laterally, the middle ear is bounded by the tympanic membrane and medially by the bony wall of the internal ear.


Histology_Ross

Histology_Ross. The middle ear works as a full-fledged mechanical energy transformer. Its primary function is to convert sound waves (air vibrations) arriving from the external acoustic meatus into mechanical vibrations that are transmitted to the internal ear. Two openings in the medial wall of the middle ear, the oval (vestibular) window and the round (cochlear) window, are essential components in this conversion process. The tympanic membrane separates the external acoustic meatus from the middle ear.


Histology_Ross

Histology_Ross. The tympanic membrane separates the external acoustic meatus from the middle ear. The tympanic membrane is in the shape of an irregular cone, the apex of which is located at the umbo that corresponds to the tip of the manubrium of the malleus. During otoscopic examination of the normal ear, tympanic membrane is in a light gray color and a cone of light (light reflex) should reflect off its surface (Fig. 25.4). The malleus is one of three small auditory ossicles residing in the middle ear and the only one that attaches to the tympanic membrane (see Fig. 25.1). Tympanic membrane forms the medial boundary of the external acoustic meatus and the lateral wall of the middle ear (Fig. 25.5). The layers of the tympanic membrane from outside to inside are  The skin of the external acoustic meatus  A core of radially and circularly arranged collagen fibers  The mucous membrane of the middle ear


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Histology_Ross. Sound waves cause the tympanic membrane to vibrate, and these vibrations are transmitted through the ossicular chain of three small bones that link the external ear to the internal ear. petrous part of temporal bone


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Histology_Ross. petrous part of temporal bone FIGURE 25.2 • Schematic drawings showing development of the ear. a. This drawing shows the relationship of the surface ectodermderived otic vesicle to the first pharyngeal arch during the fourth week of development. b. The otic vesicle sinks deep into the mesenchymal tissue and develops into the membranous labyrinth. Note the development of the tubotympanic recess lined by endoderm into the future middle-ear cavity and auditory tube. In addition, accumulation of mesenchyme from the first and second pharyngeal arches gives rise to the auditory ossicles. c. At this later stage of development, the first pharyngeal groove grows toward the developing tubotympanic recess. The auditory ossicles assume a location inside the tympanic cavity. d. This final stage of development shows how the tympanic membrane develops from all three germ layers: surface ectoderm, mesoderm, and endoderm. Note that the wall of the otic vesicle develops into the membranous labyrinth.


Histology_Ross

Histology_Ross. Perforation of the tympanic membrane may cause transient or permanent hearing impairment. The auditory ossicles connect the tympanic membrane to the oval window. The three auditory ossicles, or bones—the malleus, the incus, and the stapes—cross the space of the middle ear in series (Fig. 25.6) and connect the tympanic membrane to the oval window. These bones work like a lever system that increases the force transmitted from the vibrating tympanic membrane to the stapes by decreasing the ratio of their oscillation amplitudes. The ossicles help to convert sound waves to mechanical (hydraulic) vibrations in tissues and fluid-filled chambers. Movable synovial joints connect the bones, which are named according to their approximate shape:  The malleus (hammer) attaches to the tympanic mem brane and articulates with the incus.


Histology_Ross

Histology_Ross.  The incus (anvil), is the largest of the ossicles and links the malleus to the stapes. The stapes (stirrup), the footplate of which fits into the oval window, acts like a small piston on the cochlear fluid. Diseases that affect the external acoustic meatus, tympanic membrane, or ossicles are responsible for the conductive hearing loss (see Clinical Folders 25.1 and 25.2). Two muscles attach to the ossicles and affect their movement. The tensor tympani muscle lies in a bony canal above the auditory tube; its tendon inserts on the malleus. Contraction of this muscle increases tension on the tympanic membrane. The stapedius muscle lies in a bony eminence on the posterior wall of the middle ear; its tendon inserts on the stapes. Contraction of the stapedius tends to dampen the


Histology_Ross

Histology_Ross. FIGURE 25.3 • Horizontal section of a human temporal bone. The relationships of the three divisions of the ear within the temporal bone are shown. The tympanic membrane (TM) separates the external acoustic meatus from the tympanic cavity (TC). Within the tympanic cavity, sections of the malleus (M) and incus (I) can be seen. The posterior wall of the tympanic cavity is associated with the mastoid air cells (AC). The lateral wall of the cavity is formed principally by the tympanic membrane. The opening to the internal ear or oval window (arrowhead) is seen in the medial wall of the cavity (the stapes has been removed). The facial nerve (F) can be observed near the oval window. The cochlea (C), the vestibule (V ), and a portion of the lateral semicircular canal (LSC) of the bony labyrinth are identified. The cochlear and vestibular divisions of cranial nerve VIII (N) can also be observed within the internal acoustic meatus. 65. lateral process of malleus manubrium of malleus


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Histology_Ross. lateral process of malleus manubrium of malleus FIGURE 25.4 • The tympanic membrane in otoscopic examination of the external ear. This photograph shows the left tympanic membrane seen with otoscope during examination of the external acoustic meatus. The landmarks of tympanic membrane include the manubrium of the malleus with its visible attachment to the tympanic membrane, umbo at the tip of the manubrium, and projecting lateral process of the malleus. Note the cone of light (light reflex) that is usually seen extending anteroinferiorly from the umbo of tympanic membrane. (Courtesy of Dr. Eric J. Moore, Mayo Clinic, Rochester, MN.) movement of the stapes at the oval window. The stapedius is only a few millimeters long and is the smallest skeletal muscle.


Histology_Ross

Histology_Ross. The two muscles of the middle ear are responsible for a protective reflex called the attenuation reﬂex. Contraction of the muscles makes the chain of ossicles more rigid, thus reducing the transmission of vibrations to the internal ear. This reflex protects the internal ear from the damaging effects of very loud sound. The auditory tube connects the middle ear to the nasopharynx. The auditory (Eustachian) tube is a narrow flattened channel approximately 3.5 cm long. This tube is lined with ciliated pseudostratified columnar epithelium, about one fifth of which is composed of goblet cells. It vents the middle ear, equalizing the pressure of the middle ear with atmospheric pressure. The walls of the tube are normally pressed together but separate during yawning and swallowing. It is common for infections to spread from the pharynx to the middle ear via the auditory tube (causing


Histology_Ross

Histology_Ross. FIGURE 25.5 • Cross section through a human tympanic membrane. This photomicrograph shows the tympanic membrane, external acoustic meatus, and tympanic cavity. 9. Inset. Higher magnification of the tympanic membrane. The outer epithelial layer of the membrane consists of stratified squamous epithelium (SSE), and the inner epithelial layer of the membrane consists of low simple cuboidal epithelium (SCE). A middle layer of connective tissue (CT ) lies between the two epithelial layers. 190. otitis media). A small mass of lymphatic tissue, the tubal tonsil, is often found at the pharyngeal orifice of the auditory tube. The mastoid air cells extend from the middle ear into the temporal bone.


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Histology_Ross. The mastoid air cells extend from the middle ear into the temporal bone. A system of air cells projects into the mastoid portion of the temporal bone from the middle ear. The epithelial lining of these air cells is continuous with that of the tympanic cavity and rests on periosteum. This continuity allows infections in the middle ear to spread into these cells, causing mastoiditis. Before the development of antibiotics, repeated episodes of otitis media and mastoiditis usually led to deafness. The internal ear consists of two labyrinthine compartments, one contained within the other. The bony labyrinth is a complex system of interconnected cavities and canals in the petrous part of the temporal bone. The membranous labyrinth lies within the bony labyrinth and consists of a complex system of small sacs and tubules that also form a continuous space enclosed within a wall of epithelium and connective tissue.


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Histology_Ross. There are three fluid-filled spaces in the internal ear:  Endolymphatic spaces are contained within the membranous labyrinth. The endolymph of the membranous labyrinth is similar in composition to intracellular ﬂuid (it has a high K concentration and a low Na concentration).  The perilymphatic space lies between the wall of the bony labyrinth and the wall of the membranous labyrinth. The perilymph is similar in composition to extracellular ﬂuid (it has a low K concentration and a high Na concentration).  The cortilymphatic space lies within the organ of Corti. It is a true intercellular space. The cells surrounding the space loosely resemble an absorptive epithelium. The cortilymphatic space is filled with cortilymph, which has a composition similar to that of extracellular ﬂuid. Structures of the Bony Labyrinth The bony labyrinth consists of three connected spaces within the temporal bone. The three spaces of the bony labyrinth, as illustrated in Figure 25.7, are the:


Histology_Ross

Histology_Ross. Structures of the Bony Labyrinth The bony labyrinth consists of three connected spaces within the temporal bone. The three spaces of the bony labyrinth, as illustrated in Figure 25.7, are the: FIGURE 25.6 • Photograph of the three articulated human auditory ossicles. The three ossicles are the malleus, the incus, and the stapes. 30. The vestibule is the central space that contains the utricle and saccule of the membranous labyrinth. The vestibule is the small oval chamber located in the center of the bony labyrinth. The utricle and saccule of the membranous labyrinth lie in elliptical and spherical recesses, respectively. The semicircular canals extend from the vestibule posteriorly, and the cochlea extends from the vestibule anteriorly. The oval window into which the footplate of the stapes inserts lies in the lateral wall of the vestibule. The semicircular canals are tubes within the temporal bone that lie at right angles to each other.


Histology_Ross

Histology_Ross. The semicircular canals are tubes within the temporal bone that lie at right angles to each other. Three semicircular canals, each forming about three quarters of a circle, extend from the wall of the vestibule and return to it. The semicircular canals are identified as anterior, posterior, and lateral and lie within the temporal bone at approximately right angles to each other. They occupy three planes in space— sagittal, frontal, and horizontal. The end of each semicircular canal closest to the vestibule is expanded to form the ampulla (Fig. 25.8a). The three canals open into the vestibule through five orifices; the anterior and posterior semicircular canals join at one end to form the common bony limb (see Fig. 25.8a). The cochlea is a cone-shaped helix connected to the vestibule.


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Histology_Ross. The cochlea is a cone-shaped helix connected to the vestibule. The lumen of the cochlea, like that of the semicircular canals, is continuous with that of the vestibule. It connects to the vestibule on the side opposite the semicircular canals. Between its base and the apex, the cochlea makes about 2.75 turns around a central core of spongy bone called the modiolus (Plate 108, page 946). A sensory ganglion, the spiral ganglion, lies in the modiolus. A thin membrane (the secondary tympanic membrane) covers one opening of the canal, the round window on its inferior surface near the base. Structures of the Membranous Labyrinth The membranous labyrinth contains the endolymph and is suspended within the bony labyrinth. The membranous labyrinth consists of a series of communicating sacs and ducts containing endolymph. It is  FOLDER 25.1 Clinical Correlation: Otosclerosis


Histology_Ross

Histology_Ross. Otosclerosis is one of most common causes of acquired hearing loss. It is reported that about 13% of the U.S. population has nonclinical otosclerosis (histologic oto-sclerosis); however, incidence of clinical disease ranges from 0.5% to 1.0%. Individuals with otosclerosis complain about progressive hearing loss. Symptoms usually become apparent between ages 20 and 45. Otosclerosis is a metabolic bone disease that uniquely affects the temporal bone and ossicles and is characterized by abnormal bone remodeling. The stimulus to initiate bone remodeling in oto-sclerosis is still unknown, but recent studies associate this event with measles virus infection. Mature bone in the area of the oval window on the medial wall of the tympanic cav-ity, which separates the middle ear from the internal ear, is removed by osteoclasts and replaced with much thicker immature (woven) bone. Since the footplate of the stapes normally resides and freely vibrates within the oval window to allow the


Histology_Ross

Histology_Ross. ear, is removed by osteoclasts and replaced with much thicker immature (woven) bone. Since the footplate of the stapes normally resides and freely vibrates within the oval window to allow the transmission of sound into the internal ear, the bone remodeling in this area results in fixation of the stapes into the surrounding bone. The cemented (or frozen in place) stapes does not vibrate and prevents sound waves from reaching the perilymphatic fluid space of the internal ear, causing conductive hearing loss. The treatment of otosclerosis includes several options: phar-macologic treatment to suppress bone remodeling with fluorides and bisphosphonates, amplification of sounds with hearing aids, and surgical removal of the stapes (stapedectomy) with subsequent implantation of a pros-thesis between the incus and the oval window. Surgery is usually the most effective method of managing otosclero-sis; more than 90% of patients experience complete elim-ination of conductive hearing loss.


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Histology_Ross.  FOLDER 25.2 Clinical Correlation: Hearing Loss—Vestibular Dysfunction


Histology_Ross

Histology_Ross. Several types of disorders can affect the auditory and vestibular system and result in deafness, dizziness (vertigo), or both. Auditory disorders are classified as either sen-sorineural or conductive. Conductive hearing loss results when sound waves are mechanically impeded from reaching the auditory sensory receptors within the internal ear. This type of hearing loss principally involves the external ear or structures of the middle ear. Conductive hearing loss is the second most common type of loss after sensorineural hear-ing loss, and it usually involves a reduction in sound level or the inability to hear faint sounds. A conductive hearing loss may be caused by otitis media (ear infection); in fact, this is the most common cause of temporary hearing loss in chil-dren. Fluid that collects in the tympanic cavity can also cause significant hearing problems in children. Other com-mon causes of conductive hearing loss include excess wax or foreign bodies in the external acoustic meatus


Histology_Ross

Histology_Ross. in the tympanic cavity can also cause significant hearing problems in children. Other com-mon causes of conductive hearing loss include excess wax or foreign bodies in the external acoustic meatus or dis-eases that affect the ossicles in the middle ear (otosclero-sis; see also Folder 25.1). In many cases, conductive hearing loss can be treated either medically or surgically and may not be permanent. Sensorineural hearing impairment may also occur after injury to the auditory sensory hair cells within the inter-nal ear, cochlear division of cranial nerve VIII, nerve path-ways in the CNS, or auditory cortex. Sensorineural hearing loss accounts for about 90% of all hearing loss. It may be congenital or acquired. Causes of acquired sensorineural hearing loss include infections of the membranous labyrinth (e.g., meningitis, chronic otitis media), fractures of the tem-poral bone, acoustic trauma (i.e., prolonged exposure to excessive noise), and administration of certain classes of


Histology_Ross

Histology_Ross. membranous labyrinth (e.g., meningitis, chronic otitis media), fractures of the tem-poral bone, acoustic trauma (i.e., prolonged exposure to excessive noise), and administration of certain classes of antibiotics and diuretics. Another example of sensorineural hearing loss often re-sults from aging. Sensorineural hearing loss not only in-volves a reduction in sound level; it also affects the ability to hear clearly or to distinguish speech. A loss of the sensory hair cells or associated nerve fibers begins in the basal turn of the cochlea and progresses apically over time. The char-acteristic impairment is a high-frequency hearing loss termed presbycusis (see presbyopia, page 915). In selected patients, the use of a cochlear implant can partially restore some hearing function. The cochlear implant is an electronic device consisting of an external microphone, amplifier, and speech processor linked to a receiver implanted under the skin of the mastoid region. The receiver is con-nected


Histology_Ross

Histology_Ross. implant is an electronic device consisting of an external microphone, amplifier, and speech processor linked to a receiver implanted under the skin of the mastoid region. The receiver is con-nected to the multielectrode intracochlear implant inserted along the wall of the cochlear canal. After considerable train-ing and tuning of the speech processor, the patient’s hearing can be partially restored to various degrees ranging from recognition of critical sounds to the ability to converse.


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Histology_Ross. suspended within the bony labyrinth (Fig. 25.8b), and the remaining space is filled with perilymph. The membranous labyrinth is composed of two divisions: the cochlear labyrinth and the vestibular labyrinth (Fig. 25.8c). FIGURE 25.7 • Photograph of a cast of the bony labyrinth of the internal ear. The cochlear portion of the bony labyrinth appears blue-green; the vestibule and semicircular canals appear orange-red. (Courtesy of Dr. Merle Lawrence.) The vestibular labyrinth contains the following:  Three semicircular ducts lie within the semicircular canals and are continuous with the utricle.  The utricle and the saccule, which are contained in recesses in the vestibule, are connected by the membranous utriculosaccular duct. The cochlear labyrinth contains the cochlear duct, which is contained within the cochlea and is continuous with the saccule (see Fig. 25.8b and Fig. 25.8c). Sensory Cells of the Membranous Labyrinth


Histology_Ross

Histology_Ross. Sensory Cells of the Membranous Labyrinth Specialized sensory cells are located in six regions in the membranous labyrinth. Six sensory regions of membranous labyrinth are composed of sensory hair cells and accessory supporting cells. These regions project from the wall of the membranous labyrinth into the endolymphatic space in each internal ear (see Fig. 25.7c):  Three cristae ampullaris (ampullary crests) are located in the membranous ampullae of the semicircular ducts. They are sensitive to angular acceleration of the head (i.e., turning the head).  Two maculae, one in the utricle (macula of utricle) and the other in the saccule (macula of saccule), sense the position of the head and its linear movement.  The spiral organ of Corti projects into the endolymph of the cochlear duct. It functions as the sound receptor.


Histology_Ross

Histology_Ross.  The spiral organ of Corti projects into the endolymph of the cochlear duct. It functions as the sound receptor. FIGURE 25.8 • Diagrams of the human internal ear. a. This lateral view of the left bony labyrinth shows its divisions: the vestibule, cochlea, and three semicircular canals. The openings of the oval window and the round window can be observed.


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Histology_Ross. b. Diagram of the membranous labyrinth of the internal ear lying within the bony labyrinth. The cochlear duct can be seen spiraling within the bony cochlea. The saccule and utricle are positioned within the vestibule, and the three semicircular ducts are lying within their respective canals. This view of the left membranous labyrinth allows the endolymphatic duct and sac to be observed. c. This view of the left membranous labyrinth shows the sensory regions of the internal ear for equilibrium and hearing. These regions are the macula of the saccule and macula of the utricle, the cristae ampullaris of the three semicircular ducts, and the spiral organ of Corti of the cochlear duct. macula of saccule organ of Corti macula of utricle crista ampullaris of anterior semicircular duct crista ampullaris of lateral semicircular duct crista ampullaris of posterior semicircular duct Hair cells are epithelial mechanoreceptors of the vestibular and cochlear labyrinth.


Histology_Ross

Histology_Ross. The hair cells of the vestibular and cochlear labyrinths function as mechanoelectric transducers; they convert mechanical energy into electrical energy that is then transmitted via the vestibulocochlear nerve to the brain. The hair cells derive their name from the organized bundle of rigid projections at their apical surface. This surface holds a hair bundle that is formed of rows of stereocilia called sensory hairs. The rows increase in height in one particular direction across the bundle (Fig. 25.9). In the vestibular system, each hair cell possesses a single true cilium called a kinocilium, which is located behind the row of longest stereocilia (Fig. 25.10). In the auditory system, the hair cells lose their cilium during development but retain the basal body. The position of the kinocilium (or basal body) behind the longest row of stereocilia defines the polarity of this asymmetric hair bundle. Therefore, movement of the stereocilia toward the kinocilium is perceived differently


Histology_Ross

Histology_Ross. (or basal body) behind the longest row of stereocilia defines the polarity of this asymmetric hair bundle. Therefore, movement of the stereocilia toward the kinocilium is perceived differently than movement in the opposite direction (see below).


Histology_Ross

Histology_Ross. Stereocilia of hair cells are rigid structures that contain mechanoelectric transducer channel proteins at their distal ends.


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Histology_Ross. The stereocilia of hair cells have a molecular structure similar to those described on page 110. Tightly packed actin filaments cross-linked by fimbrin and espin (actin-bundling proteins) form their internal core structure. The high density of actin filaments and the extensive cross-linking pattern imparts rigidity and stiffness to the shaft of the stereocilium. The shaft tapers at its proximal end near the apical surface of the cell, where the core filaments of each stereocilium are anchored within the terminal web (cuticular plate). When stereocilia are deflected, they pivot at their proximal ends like stiff rods (see Fig. 25.10). Transmission electron microscope examination of the distal free end of the stereocilium reveals an electron-dense plaque at the cytoplasmic site of the plasma membrane. This plaque represents mechanoelectric transducer (MET) channel protein. A fibrillar cross-link called the tip link connects the tip of the stereocilium with the shaft of an adjacent


Histology_Ross

Histology_Ross. plasma membrane. This plaque represents mechanoelectric transducer (MET) channel protein. A fibrillar cross-link called the tip link connects the tip of the stereocilium with the shaft of an adjacent longer stereocilium (see Fig. 25.10). The tip link plays an important role in activating the MET channels at the tip of the stereocilia and opening additional transduction K channels at the site of its attachment to the shaft of neighboring stereocilium (see Fig. 25.10). The molecular structures of the transduction K channels and tip links are as yet unknown. Individual stereocilia are also connected by a variety of fibrillar extracellular cross-links.


Histology_Ross

Histology_Ross. A mutation that disrupts the gene that produces espin causes cochlear and vestibular symptoms in experimental mice. They lose their hearing early in life; these animals also spend most of their time walking or spinning in circles. The stereocilia of these animals do not maintain the rigidity necessary for proper functioning of the MET channels. All hair cells use mechanically gated ion channels to generate action potentials. All hair cells of the internal ear appear to function by moving (pivoting) their rigid stereocilia. Mechanoelectric transduction


Histology_Ross

Histology_Ross. FIGURE 25.9 • Electron micrographs of the kinocilium and stereocilia of a vestibular sensory hair cell. a. Scanning electron micrograph of the apical surface of a sensory hair cell from the macula of the utricle. Note the relationship of the kinocilium (K) to the stereocilia (S). 47,500. (Reprinted with permission from Rzadzinska AK, Schneider ME, Davies C, Riordan GP, Kachar B. An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal. J Cell Biol 2004;164:887-897.) b. Transmission electron micrograph of the kinocilium (K) and stereocilia (S) of a vestibular hair cell in cross section. The kinocilium has a larger diameter than the stereocilia. 47,500. (Reprinted with permission from Hunter-Duvar IM, Hinojosa R. Vestibule: sensory epithelia. In: Friedmann I, Ballantyne J, eds. Ultrastructural Atlas of the Inner Ear. London: Butterworth, 1984.) occurs in stereocilia that are deflected toward its tallest edge (toward the kinocilium if


Histology_Ross

Histology_Ross. In: Friedmann I, Ballantyne J, eds. Ultrastructural Atlas of the Inner Ear. London: Butterworth, 1984.) occurs in stereocilia that are deflected toward its tallest edge (toward the kinocilium if present). This movement exerts tension on the fibrillar tip links, and the generated force is used to open mechanically gated ion channels near the tip of the stereocilium. This allows for an influx of K, causing depolarization of the receptor cell. This depolarization results in the opening of voltage-gated Ca2 channels in the basolateral surface of the hair cells and the secretion of a neurotransmitter that generates an action potential in afferent nerve endings. Movement in the opposite direction (away from the kinocilium) closes the MET channels, causing hyperpolarization of the receptor cell. The means by which stereocilia are deflected varies from receptor to receptor; these are discussed in the sections describing each receptor area.


Histology_Ross

Histology_Ross. Two types of hair cells are present in the vestibular labyrinth. Both hair cell types are associated with afferent and efferent nerve endings (Fig. 25.10). Type I hair cells are flask-shaped, with a rounded base and thin neck, and are surrounded by an afferent nerve chalice and a few efferent nerve fibers. Type II hair cells are cylindrical and have afferent and efferent bouton nerve endings at the base of the cell (see Fig. 25.10). Sensory Receptors of the Membranous Labyrinth Cristae ampullaris are sensors of angular movements of the head. Each ampulla of the semicircular duct contains a crista ampullaris, which is a sensory receptor for angular movements of the head (see Figs. 25.8c and 25.11). The crista ampullaris is a thickened transverse epithelial ridge that is oriented perpendicularly to the long axis of the semicircular canal and consists of the epithelial hair cells and supporting cells (Plate 108, page 946).


Histology_Ross

Histology_Ross. A gelatinous protein–polysaccharide mass, known as the cupula, is attached to the hair cells of each crista (see Fig. 25.11). The cupula projects into the lumen and is surrounded by endolymph. During rotational movement of the head, the walls of the semicircular canal and the membranous semicircular ducts move, but the endolymph contained within the ducts tends to lag behind because of inertia. The cupula, projecting into the endolymph, is swayed by the


Histology_Ross

Histology_Ross. FIGURE 25.10 • Diagram of two types of sensory hair cells in the sensory areas of the membranous labyrinth. The type I hair cell has a flask-shaped structure with a rounded base. The base is enclosed in a chalicelike afferent nerve ending that has several synaptic boutons for efferent nerve endings. Note the apical surface specializations of this cell, which include a kinocilium and hair bundle. The apical cytoplasm of hair cells contains basal bodies for the attachment of the kinocilium and a terminal web for the attachment of stereocilia. The type II hair cell is cylindrical and possesses several nerve terminals at its base for both afferent and efferent nerve fibers. The apical surface specializations are identical to those of the type I cell. The molecular organization of the stereocilia is depicted in the enlarged rectangle. The top link connects the lateral plasma membrane of the stereocilium shaft (where K transduction channels are located) with the tip of the shorter