FIGURE 4-16

Synaptic contacts among bipolar, amacrine, and ganglion cells in inner plexiform layer. Bipolar axonal endings: A, axodendritic endings at a dyad; B, axosomatic ending on ganglion cell; C, bipolar axon-amacrine soma contact. Amacrine cell contacts with other cells; D, axoaxonal contact between bipolar and amacrine cell processes; E, axodendritic contact between amacrine and ganglion cell; F, axosomatic contact between amacrine cell process and soma of ganglion cell. (From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.)

detection and changes in brightness, as well as recognition of contrast and hue begin in this layer.78

Ribbon synapses in the IPL involve contact among a bipolar axon and a pair of postsynaptic processes, which may be amacrine or ganglion.8,79 A reciprocal synapse, thought to be inhibitory, involves the second contact of an amacrine process with a bipolar axon, providing negative feedback.52 Gap junctions between amacrine cells are also located in the IPL. Some displaced amacrine and ganglion cell bodies may also be seen.

GANGLION CELL LAYER

The ganglion cell layer is generally a single cell thick except near the macula, where it might be 8 to 10 cells thick, and at the temporal side of the optic disc, where

it is 2 cells thick. Although lying side by side, ganglion cells are separated from each other by glial processes of Müller cells.72 Displaced amacrine cells, which send their processes outward, may be found in the ganglion cell layer, as may some displaced Müller cell bodies and astroglial cells.8 Toward the ora serrata, the number of ganglion cells diminishes, and the nerve fiber layer thins.

NERVE FIBER LAYER

The nerve fiber layer (NFL; also stratum opticum) consists of ganglion cell axons. Their course runs parallel to the retinal surface; the fibers proceed to the optic disc, turn at a right angle, and exit the eye through the lamina cribrosa as the optic nerve. The fibers generally are unmyelinated within the retina. The NFL is thickest at the margins of the optic disc, where all the fibers accumulate. The group of fibers that radiate to the disc from the macular area is called the papillomacular bundle. This important grouping of fibers carries the information that determines visual acuity.

The retinal vessels, including the superficial capillary network, are located primarily in the NFL but may lie partly in the ganglion cell layer. Processes of Müller cells are common in the NFL, where they ensheathe vessels and nerve fibers.

Clinical Comment: Retinal

Hemorrhages

HEMORRHAGES  from retinal vasculature have a characteristic appearance. Because of the arrangement of the nerve fibers, the blood pools in a feathered pattern called a flame-shaped hemorrhage, which is indicative of the NFL location. Hemorrhages in the inner nuclear layer usually appear rounded and often are called dot or blot hemorrhages (Figure 4-17).

INTERNAL LIMITING MEMBRANE

The internal limiting membrane (inner limiting membrane) forms the innermost boundary of the retina. The outer retinal surface of this membrane is uneven and is composed of extensive, expanded terminations of Müller cells (often called footplates) covered by a basement membrane. The inner or vitreal surface is smooth. The connection between this membrane and the vitreous is still under investigation and may actually occur at a biochemical level (see Chapter 6); only in the periphery are vitreal fibers incorporated into the internal limiting membrane.52

Anteriorly, the internal limiting membrane of the retina is continuous with the internal limiting membrane of the ciliary body. It is present over the macula but undergoes modification at the optic disc, where processes from astrocytes replace those of the Müller cells.58

FIGURE 4-17

Fundus photo, OD, from patient with nonproliferative diabetic retinopathy exhibiting scattered dot and blot hemorrhages. (Courtesy Pacific University Family Vision Center, Forest Grove, Ore.)

FIGURE 4-18

Normal fundus of the right eye of a teenager.  The sheen from the internal limiting membrane is visible as a macular reflection. (Courtesy Pacific University Family Vision Center, Forest Grove, Ore.)

Clinical Comment: Fundus View

of the Internal Limiting Membrane

Reflections from the internal limiting membrane produce the retinal sheen seen with the ophthalmoscope. In younger persons, this membrane gives off many reflections and appears glistening; the sheen is less evident in older individuals (Figure 4-18).

R E T I N A L F U N C T I O N

Light passes through most of the retinal layers before reaching and stimulating the photoreceptor outer segment discs. The neural flow then proceeds back through the retinal elements in the opposite direction of the incident light. The efficient and accurate performance of the retina is not hampered by this seemingly reversed situation.

PHYSIOLOGY OF THE RPE

The RPE fosters the health of the neural retina and the choriocapillaris in several ways. First, the zonula occludens joining the RPE cells are part of the bloodretinal barrier and selectively control movement of nutrients and metabolites from the choriocapillaris into the retina and removal of waste products from the retina into the choriocapillaris.80 (In this regard, the RPE is analogous to the epithelium of the choroid plexus in the ventricles of the brain.)

A proposed model for RPE ion transport is shown in Figure 4-19. Ion movement occurs by Na+/K+ ATPase pumps, Na+/K+/2Cl− and Na+/2HCO3− cotransporters, Na+/H+ and Cl−/HCO3− exchangers, and gated and ungated ion channels.81 A proton-lactate-water cotransporter moves a significant amount of lactate (the product of anaerobic metabolism) across the RPE layer.81,82 Water passage occurs through aquaporins and Cl− and K+ are thought to be the primary ions driving the movement of water.83 Glucose transporters located in both the apical and basal membrane maintain a steady supply of glucose to the active photoreceptors.

Second, the RPE cells phagocytose fragments from the continual shedding of the photoreceptor outer segment discs; numerous lysosomes within each RPE cell enable it to ingest as many as 2000 discs daily.84 Undigested material accumulates as deposits of lipofuscin.81 Recently, a substance (A2E) has been identified in lipofuscin deposits that appears to inhibit RPE degradation of the outer segment remnants and contributes to RPE cell death.85 Third, the RPE metabolizes and stores vitamin A, one of the components of photopigment molecules86,87; it is the site for part of the biochemical process in the rod disc renewal system.84 Fourth, the cells contribute to the formation of the IPM between the RPE layer and the photoreceptors.75,88 Fifth, the RPE produces growth factors that drive certain cellular processes. It secretes vascular endothelial growth factor (VEGF), which helps maintain choriocapillaris function. However, the over-production of VEGF could

result in neurovascularization, and so the RPE also produces an antiangiogenic factor, pigment epithelial derived factor (PEDF); the balance between these contributes to healthy function.80 Sixth, pigment granules within the RPE cells absorb light, thereby reducing excess light scatter.

The relationship between the RPE and the photoreceptors is a reciprocal one. When either layer dysfunctions the other is ultimately affected. Retinal degenerative diseases and dystrophies often cause changes in the RPE that are clinically visible.

Clinical Comment: Retinal

Degenerations

RETINITIS PIGMENTOSA  is an autosomal dominant retinal dystrophy, resulting in a progressive loss of RPE and photoreceptor function. Both rods and cones undergo apoptosis. Rods remain functional only in the far periphery

and cones remain functional in the fovea, causing a ringlike scatomatous visual field defect. As the RPE degenerates, pigment migrates into the sensory retina, and accumulates around blood vessels in a characteristic bone-spicule pattern (Figure 4-20).

Stargardt’s macular dystrophy is a hereditary autosomal recessive disorder, resulting in vision loss occurring at an early age. A defect has been identified in a gene that directs the production of a protein that

facilitates transport to and from photoreceptor cells. Early in the disease the RPE degenerates and as the disease progresses, lipofuscin-like deposits accumulate in the macular area (Figure 4-21).These deposits are yellow and fleck-shaped. Eventually the RPE atrophies and changes

to the photoreceptors follow. Vision loss is progressive and by age 50, 50% of patients affected can have reduction of visual acuity to 20/200 or worse 89

Best’s disease, also called vitelliform macular dystrophy, is a rare autosomal dominant disorder. This disease also occurs because of a malfunctioning transport protein resulting in deposits between the RPE and neural retina.90 It usually presents in childhood as a striking yellow or orange egg yolklike elevated lesion in the macula (Figure 4-22).

SCOTOPIC AND PHOTOPIC VISION

In dim light the detection by rods predominates and in bright light, color detection takes precedence. Rods are extremely sensitive in poorly lit conditions (scotopic vision), when cones are least responsive. In scotopic vision, the light-sensitive retina allows detection of objects at low levels of illumination. Its ability to recognize fine detail is poor, however, and color vision is absent; objects are seen in shades of gray.60

Cone activity dominates in photopic vision, when the retina is responsive to a broader range of light wavelengths. Bright illumination is necessary for the sharp visual acuity and color discrimination of photopic vision. Cones are designated, depending on the wavelength that they absorb, as red (588 nm), green (531 nm), or blue (420 nm).91

NEURAL SIGNALS

The neural signal generated by photoreceptors is modified and processed within the complex synaptic pathway through which it passes. There is a greater convergence

FIGURE 4-20

Optomap® (Marlborough, MA) showing fundus of patient with retinitis pigmentosa; bone spicule-shaped deposits of pigment are evident in sensory retina. Extent of retinal vasculature can be seen. (Courtesy of Fraser Horn, O.D., Pacific University Family Vision Center, Forest Grove, Ore.)

FIGURE 4-21

Photo showing right fundus of 20-year-old patient with Stargardt’s macular dystrophy, RPE degeneration and lipofuscin depositition in the macular area. VA is reduced to 20/80. (Courtesy of JP Lowery, O.D., Pacific University Family Vision Center, Forest Grove, Ore.)

of rods than of cones onto a ganglion cell. The ratio of rods to ganglion cells is high in most retinal regions, resulting in tremendous sensitivity for the detection of light and motion. It is estimated that 75,000 rods drive 5000 rod bipolar cells and 250 AII amacrine cells before converging onto a single ganglion cell.92 A relatively small number of cones drive the cone bipolar cell, and a small number of cone bipolar cells drive a single ganglion cell. In some situations, there is a 1:1 ratio between cones and ganglion cells, reflecting the significant amount of detail that the cone population can discriminate.1 A single midget bipolar dendrite may contact only one cone pedicle, and its axon then synapses on a single midget ganglion cell.92 The cone pathway involves a three-neuron chain, whereas the rod pathway involves a four-neuron chain because of the amacrine cell inclusion.2

Ganglion cell axons can be thought of as “carrying information in processing streams,” such that certain types of information are directed toward specific destinations.8 One major target is the lateral geniculate nucleus, wherein some axons terminate in the parvocellular layers, which process wavelength, shape, fine detail, and resolution of contrast. Other axons end in the magnocellular layers, which discern movements and flickering

FIGURE 4-22

Photo showing right fundus of patient with Best’s disease; tissue disruption and mottling are evident in macular area. (Courtesy of James Kundart, O.D. and Jennifer Schumacher, Pacific University Family Vision Center, Forest Grove, Ore.)

light but have poor wavelength sensitivity­ .93 Visual information terminating in the midbrain is important in the autonomic control of the ciliary and iris muscles. Other centers that receive visual information can influence motor pathways that control eye, head, and neck movements.