SENSORY ORGANS: VISION AND HEARING

Development of the eye ( 9-2 and 9-3 )

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.

• 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 (see 9-2 ). The surface ectoderm of the head invaginates into the optical vesicle, forming a lens vesicle , which 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 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 (see 9-3 ; see Box 9-A ). 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 , which 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 , linked to the sinus venosus of the sclera , a small vein encircling the eye at the anterior edge of the choroid coat or tunica.

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 ( 9-4 )

The sclera 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 ( 9-5 )

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:

• 1.

  The corneal epithelium .

• 2.

  The layer or membrane of Bowman .

• 3.

  The stroma or substantia propria .

• 4.

  The membrane of Descemet .

• 5.

  The corneal endothelium .

The corneal epithelium is a non-keratinized stratified squamous epithelium 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 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.

The cytoplasm of the basal layer cells express keratin 5 and keratin 14 (K5 and K14), which are replaced in the upper layers by corneal-specific K3 and K12.

Corneal epithelial cells undergo continuous renewal from limbus stem cells (LSC) . LSC migrate transversely from the limbus toward the central cornea. A deficiency in LSC changes the cornea into a non-transparent, keratinized skin-like epithelium, leading to partial or complete blindness.

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 outermost 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 , which 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-B ).

Middle tunic: Uvea ( 9-6 to 9-8 ; see 9-4 )

The uvea forms the pigmented vascularized tunic of the eye and is divided into three regions (see 9-4 ; see Box 9-C ):

• 1.

  The choroid .

• 2.

  The ciliary body .

• 3.

  The iris .

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

• 1.

  Bruch's membrane , the innermost component of the choroid, consists of a network of collagen and elastic fibers and basal lamina material. Basal laminae derive from the pigmented epithelium of the retina and the endothelia of the underlying fenestrated capillaries.

• 2.

  The choriocapillaris contains fenestrated capillaries, which supply oxygen and nutrients to the outer layers of the retina and the fovea.

• 3.

  The choroidal stroma consists of large arteries and veins surrounded by collagen and elastic fibers, fibroblasts, a few smooth muscle cells, neurons of the autonomic nervous system and melanocytes.

The ciliary body 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 .

• 2.

  The neuroepithelial portion .

The uveal portion of the ciliary body includes:

• 1.

  The continuation of the outer layer of the choroid, known as the supraciliaris .

• 2.

  The ciliary muscle , a ring of smooth muscle tissue, which, when contracted, reduces the length of the circular suspensory ligaments of the lens; this is known as the ciliary zonule .

• 3.

  A layer of fenestrated capillaries supplying blood to the ciliary muscle.

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

• 1.

  An outer pigmented epithelial layer , continuous with the retinal pigmented epithelium. The pigmented epithelial layer is supported by a basal lamina continuous with Bruch's membrane.

• 2.

  An inner non-pigmented epithelial layer , which is continuous with the sensory retina.

Particular features of these two pigmented and non-pigmented epithelial cell layers include the following:

• 1.

  The apical surfaces of the pigmented and non-pigmented cells face each other .

• 2.

  The dual epithelium is smooth at its posterior end (pars plana) and folded at the anterior end (pars plicata) to form the ciliary processes .

• 3.

  The aqueous humor is secreted by epithelial cells of the ciliary processes supplied by fenestrated capillaries (see 9-8 ).

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 (see 9-7 ):

• 1.

  The anterior uveal or stromal face.

• 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 pigmented cell layers . The outer layer, a continuation of the pigmented layer of the ciliary epithelium, consists of myoepithelial cells , which 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 ( 9-9 to 9-10 ; see 9-1 )

The eye contains three chambers:

• 1.

  The anterior chamber .

• 2.

  The posterior chamber .

• 3.

  The vitreous cavity .

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 (see 9-9 and 9-10 ).

The posterior chamber (see 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 is the largest component of the eye. The longest part of the optical path from the cornea to the retina is through the vitreous humor.

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 ( 9-11 )

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 (see 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 , which extend posteriorly up to the equatorial region. In the cortical region of the lens , elongated and concentrically arranged cells (called cortical lens fiber cells) arise from the anterior epithelium at the equator region . A cortical lens fiber cell contains a nucleus and organelles. The nuclei and organelles eventually disappear when the cortical lens fiber cells approach the center of the lens, the nuclear lens fiber cell region .

Lens fiber cell differentiation consists of the expression of connexin 43 (Cx43), Cx46 and Cx50 and unique cytoskeletal proteins such as:

• 1.

  Filensin , an intermediate filament, which contains attachment sites for crystallins.

• 2.

  Lens-specific proteins called crystallins (α, βandγ). Filensin and crystallins maintain the conformation and transparency of the lens fiber cells (see Box 9-D ).

  Box 9-D

  Cataracts

  • Cataracts are an opacity of the lens caused by a change in the solubility of lens proteins as they age. This condition causes high light scattering by the aggregated filensin and crystallins and impairs accurate vision. Cataracts can be cortical, nuclear or posterior subcapsular. Most age-related cataracts are cortical cataracts.

  • Cataracts absorb and scatter more light than the normal regions of the lens, producing more light spread and a decrease in contrast of the retinal image. The result is reduced visual acuity.

  • Cataract surgery consists of a small incision made through the peripheral cornea behind the canal of Schlemm. After opening the anterior lens capsule with a cutting tool, the anterior cortex and nucleus are removed through a suction line. The posterior capsule is left intact. A flexible silicone lens, rolled up as a small tube, is inserted and opens up inside the eye to its original shape. The small incision does not require suture on completion of the procedure.

Lens fiber cells interdigitate at the medial suture region . At these contact sites, gap junctions (containing Cx46 and Cx50) interlock the opposing cytoplasmic processes. The inner cortical region and the core of the lens consist of older lens fiber cells lacking nuclei and organelles. The loss of organelles and the tight packing of the lens fiber cells contribute to minimizing light scattering. About 80% of its available glucose is metabolized by the lens.