SENSORY ORGANS: VISION AND HEARING

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9 SENSORY ORGANS: VISION AND HEARING

EYE

The eye can self-focus, adjust for light intensity, and convert light into electrical impulses interpreted by the brain. In humans, the eye is recessed in a bony orbit and is connected to the brain by the optic nerve. The eyeball protects and facilitates the function of the photoreceptive retina, the inner layer of the eyeball.

The eyeball consists of three tunics or layers which, from outside to inside, are (1) the sclera and the cornea, (2) the uvea, and (3) the retina (Figure 9-1).

Three distinct and interconnected chambers are found inside the eyeball: the anterior chamber, the posterior chamber, and the vitreous cavity (see Box 9-A). Aqueous humor circulates from the posterior to the anterior chamber. The lens is placed in front of the vitreous cavity, which contains vitreous humor. The bony orbit, the eyelids, the conjunctiva, and the lacrimal apparatus protect the eyeball.

The ophthalmic artery, a branch of the internal carotid artery, provides nutrients to the eye and the contents of the orbit. The superior and inferior orbital veins are the principal venous drainage of the eye. The veins empty into the intracranial cavernous sinus.

DEVELOPMENT OF THE EYE

A brief summary of the development of the eye is essential to the understanding of the relationship of the various layers in the eyeball. The components of the eye derive from (1) the surface ectoderm of the head; (2) the lateral neuroectodermal walls of the embryonic brain in the diencephalon region; and (3) the mesenchyme.

Lateral outpocketings of the right and left sides of the diencephalon give rise to two neuroepithelial optic vesicles, each remaining attached to the brain wall by a hollow optic stalk (Figure 9-2). The surface ectoderm of the head invaginates into the optical vesicle forming a lens vesicle that pinches off. Mesenchyme surrounds both the lens vesicle and the adjacent optic vesicle.

The optic vesicle invaginates and becomes a double-walled optic cup (see Figure 9-2). The optic fissure forms when the outer layer of the optic cup becomes the pigmented epithelium. Cells in the inner layer proliferate and stratify to form the neural retina. The mesenchyme extending into the invagination of the optic cup acquires a gelatinous consistency and becomes the vitreous component of the eye. The lens vesicle is kept in place by the free margins of the optic cup and the surrounding mesenchyme.

At the outer surface of the optic cup, the mesenchymal shell differentiates into the vascular choroid coat of the eye and the fibrous components of the sclera and cornea (Figure 9-3; see Box 9-B). Posterior to the lens, the vascular choroid coat forms the ciliary body, ciliary muscle, and ciliary processes. Anterior to the lens, the choroid coat forms the stroma of the iris. The ciliary processes secrete the aqueous humor that accumulates first in the posterior chamber (between the iris and lens) and then passes into the anterior chamber (between the lens and cornea) across the pupil. The aqueous humor leaves the anterior chamber by entering into the canal of Schlemm, a small vein (sinus venosus of the sclera) encircling the eye at the anterior edge of the choroid coat.

Around the rim of the optic cup, the inner and outer layers form the posterior epithelium of the ciliary body and iris. The sphincter and dilator pupillae muscles develop from the posterior epithelium.

The inner layer of the optic cup becomes the neural layer of the retina, which differentiates into photosensory cells, bipolar neurons, and ganglionic neurons (including interconnecting horizontal and amacrine cells and glial Müller cells). Axons from the ganglionic neurons form the nerve fiber layer of the retina, which converges on the optic stalk occupying the optic fissure as the optic nerve. The optic fissure becomes the escape route from the optic cup (except at its rim).

OUTER TUNIC: SCLERA AND CORNEA

The sclera (Figure 9-4) is a 1.0- to 0.4-mm-thick layer of collagen and elastic fibers produced by fibroblasts. The inner side of the sclera faces the choroid, from which it is separated by a layer of loose connective tissue and an elastic tissue network known as the suprachoroid lamina. Tendons of the six extrinsic muscles of the eye are attached to the outer surface of the sclera.

Cornea

The cornea is 0.8-1.1 mm thick and has a smaller radius of curvature than the sclera. It is transparent, lacks blood vessels, and is extremely rich in nerve endings. The anterior surface of the cornea is always kept wet with a film of tears retained by microvilli of the apical epithelial cells. The cornea is one of the few organs that can be transplanted without a risk of being rejected by the host’s immune system. This success can be attributed to the lack of corneal blood and lymphatic vessels.

The cornea is composed of five layers (Figure 9-5):

The corneal epithelium is stratified squamous and consists of five to seven layers of cells. Cells of the outer surface have microvilli and all cells are connected to one another by desmosomes. The cytoplasm contains cytokeratin associated with desmosomes. The epithelium of the cornea is very sensitive, contains a large number of free nerve endings, and has a remarkable wound healing capacity. At the limbus, the corneoscleral junction, the corneal epithelium is continuous with that of the conjunctiva.

Bowman’s layer is 6 to 9 μm thick, consists of type I collagen fibrils, and lacks elastic fibers. This layer is transparent and does not have regenerative capacity. Bowman’s layer is the anteriormost part of the corneal stroma, although differently organized. For this reason, it is designated “layer” instead of “membrane.” Bowman’s layer represents a protective barrier to trauma and bacterial invasion.

The highly transparent stroma or substantia propria represents about 90% of the thickness of the cornea. Bundles of types I and V collagen form thin layers regularly arranged in successive planes crossing at various angles and forming a lattice that is highly resistant to deformations and trauma. Fibers and layers are separated by an extracellular matrix rich in proteoglycans containing chondroitin and keratan sulfate.

Nerves in transit to the corneal epithelium are found in the corneal stroma.

Descemet’s membrane, one of the thickest basement membranes in the body (5 to 10 μm thick), is produced by the corneal endothelium and contains type VII collagen, which forms a hexagonal array of fibers.

The corneal endothelium lines the posterior surface of Descemet’s membrane and faces the anterior chamber of the eye. It consists of a single layer of squamous epithelial cells, with impermeable intercellular spaces preventing influx of aqueous humor into the corneal stroma. The structural and functional integrity of the corneal endothelium is vital to the maintenance of corneal transparency (see Box 9-C).

Box 9-C Corneal transplantation

This success is related to various aspects of the cornea and the ocular microenvironment: (1) The expression of major histocompatibility complex (MHC) class II is negligible or absent in the normal cornea. (2) The cornea secretes immunosuppressive factors that inhibit T cell and complement activation (see Chapter 10, Immune-Lymphatic System). (3) Cells in the cornea express Fas ligand, which protects the eye from cell-mediated damage by eliminating apoptosis cells that can determine inflammatory damage (see Apoptosis in Chapter 3, Cell Signaling). (4) Corneal Langerhans cells (see Chapter 11, Integumentary System) and antigen-presenting cells are rare in the cornea. (5) The cornea is avascular and lacks lymphatics, thus preventing the arrival of immune elements.

MIDDLE TUNIC: UVEA

The uvea forms the pigmented vascularized tunic of the eye and is divided into three regions: (1) the choroid, (2) the ciliary body, and (3) the iris (see Figure 9-7) (see Box 9-D).

The choroid consists of three layers (Figure 9-6):

The ciliary body (Figure 9-7) is anterior to the ora serrata and represents the ventral projection of both the choroid and the retina. It is made up of two components: (1) the uveal portion and (2) the neuroepithelial portion.

The uveal portion of the ciliary body includes:

The neuroepithelial portion contributes the two layers of the ciliary epithelium:

Particular features of these two pigmented and nonpigmented epithelial cell layers are:

The iris is a continuation of the ciliary body and is located in front of the lens. At this position, it forms a gate for the flow of aqueous humor between the anterior and posterior chambers of the eye and also controls the amount of light entering the eye.

The iris has two components: (1) the anterior uveal or stromal face and (2) the posterior neuroepithelial surface.

The anterior (outer) uveal face is of mesenchymal origin and has an irregular surface. It is formed by fibroblasts and pigmented melanocytes embedded in an extracellular matrix. The number of pigmented melanocytes determines the color of the iris. In albinos, the iris appears pink due to the abundant blood vessels. Blood vessels of the iris have a radial distribution and can adjust to changes in length in parallel to variations in the diameter of the pupil.

The posterior (inner) neuroepithelial surface consists of two layers of pigmented epithelium. The outer layer, a continuation of the pigmented layer of the ciliary epithelium, consists of myoepithelial cells that become the dilator pupillae muscle. The smooth muscle of the sphincter pupillae is located in the iris stroma around the pupil.

Three chambers of the eye

The eye contains three chambers (see Figure 9-1): (1) the anterior chamber, (2) the posterior chamber, and (3) the vitreous cavity. The vitreous is the largest component of the eye. The longest part of the optical path from the cornea to the retina is through the vitreous.

The anterior chamber occupies the space between the corneal endothelium (anterior boundary) and the anterior surface of the iris, the pupillary portion of the lens, and the base of the ciliary body (posterior boundary). The circumferential angle of the anterior chamber is occupied by the trabecular meshwork, a drainage site for the aqueous humor into the canal of Schlemm (Figures 9-9 and 9-10).

The posterior chamber (see Figure 9-9) is limited anteriorly by the posterior surface of the iris and posteriorly by the lens and the zonular fibers (suspensory ligaments of the lens). The circumferential angle is occupied by the ciliary processes, the site of aqueous humor production.

The vitreous cavity is occupied by a transparent gel substance–the vitreous humor—and extends from the lens to the retina. The vitreous humor contains mostly water (99%), hyaluronic acid, and type II collagen fibrils, a close relative of the collagen in cartilage. Recall from the discussion on the extracellular matrix of connective tissue that the glycosaminoglycan hyaluronic acid has significant affinity for water. Fully hydrated hyaluronic acid, associated with widely spaced collagen fibrils, is responsible for changes in vitreous volume. Hyaluronic acid and type II collagen are produced by hyalocytes.

LENS

The cornea, the three chambers of the eye, and the lens are three transparent structures through which light must pass to reach the retina. Note that the refractive surface of the cornea is an interface between air and tissue and that the lens is in a fluid environment whose refractive index is higher than that of air.

The lens is a transparent, biconvex, elastic, and avascular structure (Figure 9-11). Zonular fibers, consisting of elastin fibrils and a polysaccharide matrix, extend from the ciliary epithelium and insert at the equatorial portion of the capsule. They maintain the lens in place and, during accommodation, change the shape and optical power of the lens in response to forces exerted by the ciliary muscle. The zonular fibers support the lens “as guy wires support a tent.”

The lens consists of a series of concentric shells or layers forming the lens substance. The inner part of the lens is the nucleus. The outer part is the cortex. The anterior epithelium has a single layer of epithelial cells and is the source of new cells of the lens. The posterior epithelium disappears early in the formation of the lens. The anterior epithelium and lens substance are enclosed by the lens capsule. There is no epithelial cell layer under the posterior surface of the capsule.

The lens capsule is a thick flexible acellular and transparent basement membrane—like structure containing type IV collagen fibrils and a glycosaminoglycan matrix. Beneath the anterior portion of the capsule is a single layer of cuboidal epithelial cells that extend posteriorly up to the equatorial region. In the cortical region of the lens, elongated and concentrically arranged cells (called cortical lens fibers) arise from the anterior epithelium at the equator region. Cortical lens fibers contain a nucleus and organelles. The nucleus and organelles eventually disappear when the cortical lens fibers approach the center of the lens—the nuclear lens fiber region.

Lens cell differentiation consists of the appearance of unique cytoskeletal proteins: (1) filensin, an intermediate filament that contains attachment sites for crystallins and (2) lens-specific proteins called crystallins (α, β, and γ). Filensin and crystallins maintain the conformation and transparency of the lens fiber cell.

Lens cell fibers interdigitate at the medial suture region. At these contact sites, gap junctions and some spot desmosomes interlock the opposing cytoplasmic processes. The inner cortical region and the core of the lens consist of older lens fibers lacking nuclei. About 80% of its available glucose is metabolized by the lens.

Accommodation

The sharpness of distant and close images focused on the retina depends on the shape of the lens (Figure 9-12). Accommodation defines the process by which the lens becomes rounder to focus the image of a nearby object on the retina and flattens when the image of a distant object is focused on the retina.

Accommodation determines that the distance between the center of the lens and the retina is equivalent to the focal distance needed for the formation of a sharp image on the retina.

Three components contribute to the accommodation process: (1) the ciliary muscle, (2) the ciliary body, and (3) the suspensory ligaments, inserted at the equatorial region of the lens capsule.

When the ciliary muscle contracts, the ciliary body moves toward the lens. Consequently, the tension of the suspensory ligaments is reduced, and the elastic capsule of the lens enables the lens to acquire a spherical shape. A rounded lens facilitates close vision.

When the ciliary muscle relaxes, the ciliary body keeps the tension of the suspensory ligaments that pull at the circumference of the lens. Thus, the lens remains flat to enable distant vision. This condition is known as emmetropia (Greek emmetros, in proper measure; opia, pertaining to the eye), or normal vision.

If the eyeball is too deep or the curvature of the lens is not flat enough, the image of a distant object forms in a plane in front of the retina. Distant objects are blurry because they are out of focus, but vision at close range is normal. This condition is called myopia (Greek myein, to shut), or nearsightedness.

If the eyeball is too shallow and the curvature of the lens is too flat, the distant image is formed at a plane behind the retina. Distant objects are well resolved but objects at a closer range are not. This condition is called hyperopia (Greek hyper, above), or farsightedness.

Older people become farsighted as the lens loses elasticity. This form of hyperopia is known as presbyopia (Greek presbys, old man).

Accommodation difficulties can be improved by the use of lenses. A diverging lens corrects myopia; a converging lens corrects hyperopia.

INNER LAYER: RETINA

The retina consists of two regions (Figure 9-13): (1) the outer nonsensory retinal pigmented epithelium, and (2) the inner sensory retina (see Box 9-E).

The nonsensory retinal pigmented epithelium is a single layer of cuboidal cells extending from the edge of the optic disk to the ora serrata, where it continues as the pigmented layer of the ciliary epithelium.

The apical domain of the cuboidal nonsensory pigmented epithelium is sealed by tight junctions to form the external retinal barrier (Figure 9-14). Granules of melanin are present in the apical cytoplasm and apical cell processes. Melanin granules absorb excess light reaching the photoreceptors.

The apical surface contains microvilli that surround the outer segments of the photoreceptors (cones and rods). At this location, the sensory retina and the pigmented epithelium are attached to each other through an amorphous extracellular material, the interphotoreceptor matrix (Figure 9-15).

The inner sensory retina layer extends from the edge of the optic disk to the ciliary epithelium. The sensory retina has two clinically and anatomically important landmarks to remember: (1) the fovea centralis, a shallow depression of about 2.5 mm in diameter and (2) the macula lutea, a yellow rim surrounding the fovea centralis. The fovea is the area of the retina where vision is the sharpest and is crossed by the visual axis. We discuss these structures later.

Photoreceptor neurons: Rods and cones

Rods (see Figure 9-15) and cones (Figure 9-16) occupy specific regions in the sensory retina. Cones are predominant in the fovea centralis and perceive color and detail. Rods are concentrated at the periphery and function in peripheral and night vision.

Both rods and cones are elongated cells with specific structural and functional polarity. They consist of two major segments: an outer segment and an inner segment. The outer segment contains stacks of flat membranous disks harboring a photopigment. The disks are infoldings of the plasma membrane that pinch off as they move away from the modified cilium, the outer-inner segment connecting region.

The various components of the disks are synthesized in the inner segment and are transported by molecular motors (kinesins and cytoplasmic dyneins) along microtubules toward the outer segment across the narrow cytoplasmic bridge containing the modified cilium. We discuss in Chapter 1, Epithelium, details of the mechanism of intraciliary transport.

The production and turnover of the disks is continuous. New disks are added near the cilium. Older disks move toward the pigmented epithelium of the retina and once they reach the tip of the outer segment, they are phagocytosed by the cells of the pigmented epithelium. The duration of the disk recycling process is about 10 days.

The inner segment displays abundant mitochondria—involved in the synthesis of adenosine triphosphate (ATP), the Golgi apparatus, and rough and smooth endoplasmic reticulum. The modified cilium consists of nine peripheral micro-tubule doublets but lacks the central pair of microtubules. The terminal portion of the photoreceptors is equivalent to an axon forming synaptic contacts with cytoplasmic processes—neurites—of bipolar cells and horizontal cells.

There are three significant differences between rods and cones:

3. Rods contain the photopigment rhodopsin (Figure 9-17). Cones contain a similar pigment called iodopsin. Rhodopsin operates during night vision. Iodopsin perceives detail and discriminates color (blue, green, and red). Both rhodopsin and iodopsin are transmembrane proteins bound to the prosthetic group 11-cis-retinal. The protein lacking the prosthetic group is called opsin (see Box 9-G).

There are three different photopigments in cones with different light absorbance and sensitive to blue light (420 nm), green light (535 nm), and red light 565 nm), respectively. The isomerization of 11-cis-retinal to 11-trans-retinal is identical in rods and cones.

The eyelids, conjunctiva, and the lacrimal gland

The anterior portion of the eyeball is protected by the eyelids, the conjunctiva, and the fluid produced by the lacrimal gland.

Each eyelid consists of two portions (Figure 9-22): (1) an outer cutaneous portion lined by a stratified squamous epidermis overlying a loose connective tissue dermis and skeletal muscle (orbicularis oculi muscle) and (2) an inner conjunctival portion, lined by a thin mucous membrane, the conjunctiva.

The cutaneous portion contains several skin appendages: (1) sweat and sebaceous glands and (2) three to four rows of stiff hairs, the eyelashes, at the eyelid margins. Eyelashes are associated with modified sweat glands known as the glands of Moll.

Facing the conjunctival lining is the tarsal plate, a fibroelastic dense connective tissue containing large sebaceous tarsal glands, also known as meibomian glands. Each tarsal gland opens at the margin of the eyelid. The tarsal plate is responsible for the rigidity of the eyelids.

The junction between the cutaneous and conjunctival portions is demarcated clinically by the sulcus, a gray line located between the ducts of the meibomian glands and the eyelashes.

The conjunctiva is continuous with the skin lining and extends up to the periphery of the cornea. It consists of polygonal to columnar stratified epithelial cells with mucus-secreting goblet cells. At the corneal rim, the conjunctival epithelium becomes stratified squamous and is continuous with the corneal epithelium. A lamina propria with capillaries supports the lining epithelium.

The lacrimal gland produces a fluid, tears, that first accumulate in the conjunctival sac and then exit into the nasal cavity through a drainage duct (nasolacrimal duct). Tears evaporate in the nasal cavity but can produce a sniffy nose when excessive fluid is produced.

The lacrimal gland (Figure 9-23) is a tubuloacinar serous gland with myoepithelial cells. It is organized into separate lobes with 12 to 15 independent excretory ducts. Tears enter the excretory canaliculi through the puncta and reach the nasolacrimal sac and duct to eventually drain in the inferior meatus within the nasal cavity.

Lacrimal glands receive neural input from (1) parasympathetic nerve fibers, originating in the pterygopalatine ganglion; acetycholine receptors on glandular cells respond to acetylcholine released at the nerve terminals; and (2) sympathetic nerve fibers, arising from the superior cervical ganglion.

Blinking produces gentle compression of the lacrimal glands and the release of fluid. Tears keep the surface of the conjunctiva and cornea moist and rinse off dust particles. Spreading of the mucus secreted by the conjunctival epithelial cells, the oily secretion derived from the tarsal glands, and the continuous blinking of the eyelids prevent rapid evaporation of the tear film. Tears contain lysozyme, an antibacterial enzyme; lactoferrin; secretory immunoglobulin A; and tear-specific prealbumin (see Figure 9-23).

Excess production of tears occurs in response to chemical and physical irritants of the conjunctiva, high light intensity, and strong emotions. A disruption in the production of tears or damage to the eyelids results in the drying out of the cornea (dry eye or keratoconjunctivitis sicca), which is followed by ulceration, perforation, loss of aqueous humor, and blindness.

MIDDLE EAR

The middle ear, or tympanic cavity, is an air-filled space in the temporal bone interposed between the tympanic membrane and the structures contained in the inner ear. The main function of the middle ear is the transmission of sound from the tympanic membrane to the fluid-filled structures of the inner ear.

Sound transmission is carried out by the auditory or bony ossicles (malleus, incus, and stapes) organized in a chainlike fashion by interconnecting small ligaments. In this chain, the arm of the malleus is attached to the tympanic membrane at one end; at the other end, the footplate of the stapes is applied to the oval window (fenestra vestibuli), an opening of the bony labyrinth. The tensor tympani (innervated by the trigeminal nerve [cranial nerve V]) and stapedius muscles (innervated by the facial nerve [cranial nerve VII]) keep the three auditory ossicles functionally linked.

The bony ossicles have two roles: (1) They modulate the movement of the tympanic membrane. (2) They apply force to the oval window, thus amplifying the incoming sound waves. Otosclerosis and otitis media affect the movements of the ossicles, conditions leading to hearing loss.

The tympanic cavity (also called the tubotympanic recess or sulcus) is lined by a squamous-to-cuboidal epithelium and lacks glands in the supporting connective tissue.

The tympanic membrane has an oval shape with a conical depression near the center caused by the attachment of the arm of the malleus. Two differently oriented layers of collagen fibers form the core of the membrane, and the two sides of the membrane are lined by a simple squamous-to-cuboidal epithelium.

The auditory or eustachian tube links the middle ear with the nasopharynx. Adjacent to the tympanic cavity, the tube is formed by the temporal bone. Elastic cartilage continues the bony portion of the tube, which then changes into hyaline cartilage near the nasopharynx opening. A ciliated epithelium with regional variations (low columnar-to-pseudostratified near the nasopharynx) and with mucus-secreting glands lines the bony and cartilaginous segments of the tube. The role of the auditory tube is to maintain a pressure balance between the tympanic cavity and the external environment.

Defects in middle ear development include the absence of structural elements, such as the tympanic ring, which supports the tympanic membrane and the ossicles. The tympanic ring is derived from mesenchyme of the first pharyngeal arch (malleus and incus) and second pharyngeal arch (stapes), the middle ear muscles, and the tubotympanic recess.

INNER EAR

SEMICIRCULAR CANALS

The semicircular ducts are contained within the osseous labyrinth. The three ducts are connected to the utricle. Ducts derived from the utricle and saccule join to form the endolymphatic duct. The endolymphatic duct ends in a small dilation called the endolymphatic sac, located between the layers of the meninges.

Small dilations—ampullae—are present at the semicircular duct–utricle connection sites. Each ampulla has a prominent ridge called the crista ampullaris.

The crista ampullaris (Figure 9-28) consists of a sensory epithelium covered by a gelatinous mass called the cupula. The cupula contains otogelin, a glycoprotein anchoring the cupula to the sensory epithelium.

The sensory epithelium consists of two cell types (see Figure 9-28): (1) the hair cells and (2) the supporting cells. Like all other sensory receptors, hair cells respond to sustained stimuli by adapting and restoring their sensitivity to threshold deflections on a millisecond to sub-millisecond timescale.

The basal surface of the supporting cells is attached to a basal lamina. In contrast, the hair cells occupy a recess in the apical region of the supporting cells and do not reach the basal lamina. The apical domain of the hair cells contains 60 to 100 hairlike specialized stereocilia and a single kinocilium. Stereocilia are supported by an actin-containing cuticular plate. The free ends of both stereocilia and kinocilia are embedded in the cupula. The cupula attaches to the roof and walls of the ampulla and acts like a partition of the lumen of the ampulla (see Figure 9-28).

When the position of the cupula changes in response to movements of the endolymph, it causes displacement of the stereocilia and kinocilium of the hair cells (Figure 9-29). When stereocilia move toward the kinocilium, the plasma membrane of the hair cells depolarizes and the afferent nerve fibers are stimulated (excitation). When stereocilia are deflected away from the kinocilium, the hair cell hyperpolarizes and afferent nerve fibers are not stimulated (inhibition).

The cristae have two types of hair cells: (1) type I hair cells and (2) type II hair cells.

Both cell types are essentially similar in their internal structure, but differences exist in their shape and innervation:

In addition to afferent nerves, both type I and type II hair cells receive efferent nerve terminals and have synaptic vesicles containing the neurotransmitter acetylcholine. Efferent nerve fibers control the sensitivity of the sensory receptor cells.

Supporting cells and hair cells are associated with each other by apical junctional complexes. Characteristic features of the supporting cells are an apical dense terminal web and the presence of short microvilli. Supporting cells lack stereocilia and kinocilia, two features typical of hair cells.

Clinical significance: Ménière’s disease

Secretory cells in the membranous labyrinth and the endolymphatic sac maintain the ionic balance between endolymph and perilymph (see Figure 9-36). An increase in the volume of endolymph is the cause of Ménière’s disease, which is characterized by vertigo (illusion of rotational movement in space), nausea, positional nystagmus (involuntary rhythmic oscillation of the eyes), vomiting, and ringing in the ears (tinnitus).

OTOLITHIC ORGANS: UTRICLE AND SACCULE

The utricle and saccule display a sensory epithelium called a macula (Figure 9-30). Like the sensory epithelium of the crista ampullaris in the semicircular canals, the macula contains hair cells and supporting cells. The macula is covered by a gelatinous substance containing calcium carbonate–protein complexes forming small crystals called otoliths (see Figure 9-29). Otoliths are not present in the cupula overlying the hairs of the crista ampullaris. Small ductules derived from the utricle and saccule join to form the endolymphatic duct ending in the endolymphatic sac. The ductus reuniens links the saccule to the base of the membranous cochlear duct.

COCHLEA

The cochlear duct is a membranous coiled duct inserted in the bony cochlea. It consists of an apex and a base. The coiled duct makes about two and two-thirds turns with a total length of 34 mm.

The cochlea has three spiraling chambers (Figures 9-31 to 9-33):

The scalae vestibuli and tympani are filled with perilymph and communicate at the helicotrema at the apex of the cochlea (see Figure 9-33).

In cross section, the boundaries of the scala media are the basilar membrane at the bottom, the vestibular or Reissner’s membrane above, and the stria vascularis externally. The cells and capillaries of the stria vascularis produce endolymph.

The stria vascularis has a rich supply of blood vessels and is lined by a pseudostratified epithelium consisting of basal cells (of neural crest or mesoderm origin), intermediate cells (melanocyte-like cells of neural crest origin) and marginal cells (of epithelial cell origin). Marginal cells contain an ATPase K+ pump involved in K+ release into the endolymph. Basal cells are linked to intermediate cells by gap junctions. Intermediate cells harbor Kcnj10, a potassium inwardly rectifying channel, subfamily J, member 10, that generates an endocochlear potential and membrane voltage and produces endolymph. The recycling of K+ions from the hair cells back into the endolymph maintains the appropriate high K+ concentration in the endolymph fluid, critical for normal hair cell function.

The spiraling bony core of the cochlea is the modiolus. On the inner side, the spiral osseous lamina projects outward from the modiolus to join the basilar membrane. On the external side, the basilar membrane is continuous with the spiral ligament.

The organ of Corti (Figures 9-34 and 9-35) is the sensory epithelium of the cochlea. It is formed by (1) inner and outer hair cells; (2) supporting cells; (3) the tectorial membrane, extending outward from the spiral limbus; and (4) the inner tunnel, limited by the outer and inner pillar cells, separating inner from outer hair cells.

A single line of inner hair cells extends from the base to the apex of the cochlea (see Figures 9-34 and 9-35). The outer hair cells are arranged in three parallel rows, also extending from the base to the apex of the cochlea. A hair bundle, formed by 50 to 150 stereocilia in a long-to-short gradient arrangement, extends from the apical domain of each hair cell. No kinocilium is present in the hair bundle of the cochlea.

Each member of the hair bundle consists of a core of actin filaments. The tip of the actin bundle is the site where actin monomers are added under control of myosin XVa in association with the protein whirlin. Defects in myosin Va and whirlin cause abnormally short stereocilia. At the base, the actin bundle is stabilized by the protein radixin (Figure 9-36). Stereocilia within a hair bundle are interconnected by extracellular filaments (interciliary links). Side links (myosin VIIa and associated proteins) connect stereocilia along their shafts. Tip links (cadherin 23) extend from the tip of a stereocilium to the side of the taller adjacent stereocilium. The tension of the tip link is controlled by myosin 1c. Defects in interciliary links result in Usher’s syndrome, characterized by disorganization of hair bundles leading to sensorineural deafness of cochlear origin combined with retinitis pigmentosa (loss of vision).

Interciliary links regulate the opening and closing of mechanoelectrical transduction (MET) ion channels, permeable to Ca2+. Deflection of the hair bundle toward the taller stereocilia side opens the MET channels; displacements in the opposite direction close these channels. Interciliary links ensure a uniform response of MET channels. MET Ca2+ channels are essential for the conversion of a sound stimulus to an equivalent electrical signal and frequency tuning.

The tectorial membrane is an extracellular matrix that contacts the stereocilia bundles of the outer hair cells. It contains α- and β-tectorin proteins and otogelin, also seen in the cupula (crista ampullaris) and otolithic membrane (maculae). As previously indicated, otogelin is essential for the anchoring of the cupula and otolithic membrane to the sensory epithelium. Conversely, otogelin appears to be dispensable for the anchoring of the tectorial membrane to the spiral limbus.

When the basilar membrane and organ of Corti are displaced, stereocilia of outer hair cells hit the tectorial membrane and depolarization of the hair cells occurs (see Figure 9-36).

The spiral ganglion is housed in the modiolus. Processes of the bipolar sensory neurons of the spiral ganglion extend into the osseous spiral lamina, lose their myelin, pierce the basilar membrane, and synapse on the basal domain of the inner and outer hair cells.

There are two types of bipolar sensory neurons in the spiral ganglion: (1) type I cells (90% to 95%) whose fibers contact inner hair cells and (2) type II cells (5% to 10%) that synapse with outer hair cells.

The neuronal processes of types I and II cells form the cochlear branch of the vestibulocochlear nerve. Olivocochlear efferent fibers run along the basilar membrane to contact the inner and outer hair cells. Neurons of the auditory and vestibular ganglia fail to develop when the neurogenin 1 gene is deleted.

Clinical significance: Deafness and balance

Cytoskeletal components in the apical domain of hair cells are relatively abundant. Hair cells convert mechanical input, determined by the deflection of apical bundles of stereocilia embedded in the tectorial membrane and the otolithic membrane of the cupula, into an electromechanical input leading to synaptic transmission.

In the absence of the transcription factor Pou4f3 (for POU domain, transcription factor 4, class 3), hair cells express specific markers (including unconventional myosin VI and VIIa), and both hair cells and spiral ganglion neurons degenerate.

The tectorial membrane, cupula and otolithic membrane contain α-tectorin, β-tectorin and otogelin. When the α-tectorin- and otogelin-encoding genes are mutated, deafness and imbalance occur (Figure 9-38).

A mutation in the gene for connexin 26, a component of gap junctions on the surface of supporting cells, is responsible for deafness because the recycling of endolymph K+ from the intercellular spaces to the stria vascularis is disrupted. Connexin 26 is not present in hair cells.

There are several mouse mutants with a decrease in neural crest–derived melanocytes in the stria vascularis. Although the particular role of melanocytes in the stria vascularis is not known, a mutation in the c-kit gene (encoding the stem cell factor receptor and its ligand; see Chapter 6, Blood and Hematopoiesis, for a discussion of the c-kit gene) affects the function of the stria vascularis and the mice are deaf.

Waardenburg’s syndrome in humans is an autosomal dominant type of congenital deafness associated with pigment abnormalities, such as partial albinism, and abnormal development of the vestibulocochlear ganglion. Recall that melanocytes have a common origin in the neural crest and are migratory cells.

Sensory Organs: Vision and Hearing

Essential concepts

Outer tunic: sclera and cornea. The sclera is a thick layer of collagen and elastic fibers produced by fibroblasts. The cornea is a transparent, avascular, and innervated tissue.

It consists of five layers: (1) a stratified corneal epithelium exposed to the environment, (2) a supporting membrane or layer of Bowman, (3) a regularly oriented corneal stroma, (4) the membrane of Descemet, and (5) the corneal endothelium (a simple squamous epithelium in contact with aqueous humor).

Middle tunic: uvea. The uvea consists of three regions: (1) choroid, (2) ciliary body, and (3) iris.

The choroid consists of three layers: (1) Bruch’s membrane (formed by the basal lamina of the pigmented epithelium of the retina, the basal lamina of fenestrated capillaries corresponding to the choriocapillaris, and connective tissue in between, the site of deposits of amyloid material called drusen), (2) choriocapillaris (the source of nutrients to the outer layers of the retina), and (3) the choroid stroma (containing melanocytes, blood vessels, and neurons of the autonomic nervous system).

The ciliary body, anterior to the ora serrata, consists of two portions: (1) the uveal portion (the supraciliaris portion of the choroid; the ciliary muscle, which controls the curvature of the lens by modifying the length of the suspensory ligaments; and fenestrated capillaries). (2) The neuroepithelial portion (which contributes two cell layers to the ciliary epithelium: a pigmented cell layer and a nonpigmented cell layer, continuous with the sensory retina; the apical surfaces of these two layers face each other and secrete aqueous humor).

The iris is a continuation of the ciliary body. It has an anterior surface without epithelial lining (melanocytes and fibroblasts), and a posterior surface lined by a dual layer of pigmented cells. The stroma contains myoepithelial cells (dilator pupillae muscle) and smooth muscle cells (sphincter pupillae).

The lens is a biconvex, transparent, elastic, and avascular structure kept in place by zonular fibers (extending from the ciliary epithelium and inserting at the equatorial region of the lens capsule). The lens consists of (1) a capsule, (2) an epithelium, and (3) a lens substance (consisting of cortical and nuclear lens fibers). Filensin and crystallins (α, β, and γ) are intermediate filament proteins found in the lens. Cataracts, an opacity of the lens, is caused by a change in the solubility of these proteins.

Accommodation is the process by which the lens becomes rounder (to focus the image of a nearby object on the retina) and flattens (when the image of a distant object is focused on the retina).

Accommodation involves the participation of the ciliary muscle, the ciliary body, and the suspensory ligaments. When the ciliary muscle contracts, the tension of the ligaments is reduced (because the ciliary body moves closer to the lens), and the lens acquires a spherical shape (close vision). When the ciliary muscle relaxes, the tension of the ligaments increases (the ciliary body moves away from the lens), and the lens becomes flat (distant vision).

Emmetropia is normal vision. Myopia (or nearsightedness) occurs when the eyeball is too deep or the curvature of the lens is not flat enough for distant vision; the image of a distant object forms in front of the retina. Hyperopia (or farsightedness) is when the eyeball is too shallow and the curvature of the lens is too flat; the image of a distant object forms behind the retina. Older people become farsighted as the lens loses elasticity, a condition known as presbyopia.

Inner tunic: retina. The retina consists of two regions: (1) the outer nonsensory retinal pigmented epithelium (a single layer of pigmented cuboidal cells extending from the optic disk to the ora serrata) and (2) the inner sensory retina (extending from the optic disk to the ciliary epithelium).

The separation of these two layers, resulting from trauma, vascular disease, metabolic disorders, and aging, results in detachment of the retina. The pigmented epithelium of the retina is essential for the transport of nutrients from the choroidal blood vesssels to the outer layers of the retina, the removal of waste metabolic products from the sensory retina, the phagocytosis and recycling of photoreceptor disks, and the recycling of the photobleached pigment rhodopsin. The basal lamina of the pigmented epithelium is a component of Bruch’s membrane.

The sensory retina consists of four cell groups: (1) photorecepor neurons (rods and cones), (2) conducting neurons (bipolar and ganglion cells), (3) association neurons (horizontal and amacrine cells), and (4) supporting neuroglia Müller cells. Cells are distributed in 10 layers summarized in Figure 9-14. There are three distinct nuclear regions: (1) the outer nuclear layer corresponds to the nuclei of the photoreceptors; (2) the inner nuclear layer corresponds to the nuclei of bipolar cells, horizontal and amacrine cells, and Müller cells; and (3) the ganglion layer contains the nuclei of the ganglion cells. The plexiform and limiting membranes represent sites of contacts among the retinal cells.

Photoreceptor cells (rods and cones) are elongated and consist of two segments: an outer segment, which contains flat membranous disks and an inner segment, the site of synthesis of various cell components. A modified cilium connects the outer and inner segments. It also provides microtubules for molecular motor proteins (kinesins and cytoplasmic dyneins) to deliver materials to the disk assembly site by the mechanism of intraciliary transport. The differences between rods and cones are the following: (1) the outer segment of the rod is cylindrical; in cones it is conical. (2) Rods terminate in a spherule; cones end in a pedicle. Both endings interact with bipolar and horizontal cells. (3) Rods contain the photopigment rhodopsin (night vision); cones contain a similar pigment, iodopsin (color vision).

Bipolar and ganglion cells are connecting neurons receiving impulses from photoreceptor cells.

Horizontal and amacrine cells do not have axons or dendrites, only neuritic processes conducting in both directions.

Müller cells are columnar cells that occupy the spaces between photoreceptor and bipolar and ganglion cells. Müller cells contact the outer segment of the photoreceptors, establishing zonulae adherentes and microvilli, corresponding to the outer limiting membrane. The inner limiting membrane represents the basal lamina of Müller cells.

The fovea centralis, surrounded by the macula lutea, is a specialized area for accurate vision. The optic disk (the exit site of axons derived from ganglion cells and the passage site of blood vessels), including the optic papilla, is not suitable for vision (the blind spot of the retina).

EAR

The ear consists of three portions: (1) external ear, (2) middle ear, and (3) inner ear.

The external ear consists of the auricle (external ear), which collects sound waves that are conducted across the external acoustic meatus to the tympanic membrane.

The middle ear (or tympanic cavity) is an air-filled space in the temporal bone that contains the auditory or bony ossicles (malleus, incus, and stapes). The arm of the malleus is attached to the tympanic membrane at one end; the footplate of the stapes is applied to the oval window, an opening of the bony labyrinth. Bony ossicles modulate the movement of the tympanic membrane and apply force to the oval window (to amplify the incoming sound waves). Otitis media and otosclerosis affect the movement of the ossicles and can lead to hearing loss. The auditory or eustachian tube (elastic cartilage changing to hyaline catilage) links the middle ear to the nasopharynx. It maintains a pressure balance between the tympanic cavity and the external environment.

The inner ear occupies the osseous labyrinth, which contains the membranous labyrinth. The membranous labyrinth houses the vestibular and auditory systems. The membranous labyrinth contains endolymph (high concentration of K+ and low concentration of Na+). Perilymph (high concentration of Na+ and low concentration of K+) is present between the osseous labyrinth and the membranous labyrinth.

The vestibular system consists of two sacs (utricle and saccule), and three semicircular canals (superior, horizontal, and posterior) arising from the utricle. Ampullae are present at the semicircular canal–utricle connection site.

The endolymphatic duct derives from the utricle and saccule and fuses into a single duct, which terminates in a small dilation, the endolymphatic sac, located between the layers of the meninges. An increase in the volume of endolymph causes Ménière’s disease, characterized by vertigo, nausea, positional nystagmus, vomiting, and tinnitus (ringing in the ears).

The ampulla has a crista, an elevation covered by sensory epithelium consisting of type I and II hair cells and supporting cells, topped by the cupula, a gelatinous substance surrounded by endolymph. Semicircular canals respond to rotational movements of the head and body (angular acceleration).

Hair cells have an apical domain containing 60 to 100 stereocilia (supported by an actin-containing cuticular plate) and a single kinocilium. The free ends of the stereocilia and kinocilium are embedded in the cupula.

The maculae of the utricle and saccule respond to translational movements (gravity and linear acceleration). Maculae consist of a sensory epithelium (type I and II hair cells and supporting cells) topped by the otolithic membrane, a gelatinous substance similar to cristae, except for the presence of otoliths containing calcium carbonate.

The auditory system consists of the cochlea, a coiled duct. The cochlea has three spiraling chambers: (1) the cochlear duct (called scala media), (2) the scala vesibuli, starting at the oval window, and (3) the scala tympani, ending at the round window. The scala vestibuli and scala tympani contain perilymph and communicate at the helicotrema.

The organ of Corti is the sensory epithelium of the cochlea. It contains hair cells and supporting cells. Instead of a cupula found in the crista and macula, the sensory epithelium of the cochlea is in contact with the tectorial membrane. The organ of Corti consists of two groups of hair cells: inner and outer hair cells, separated from each other by the inner tunnel, limited by outer and inner pillar cells and supported by phalangeal cells. Hair cells of the cochlea lack kinocilia but have stereocilia. The stria vascularis of the cochlear duct produces endolymph.

The modiolus, the spiraling bony axis of the cochlea, houses the spiral ganglion.

Deafness occurs when α-tectorin and otogelin are defective in the tectorial membrane, connexin 26 is not present in gap junctions linking cochlear supporting cells, and the vestibulocochlear ganglion is not developed (Waardenburg’s syndrome).