Figure 1.
(a) Normal retina. (Left) Anatomical depiction of the human eye viewed in sagittal section. Light entering the eye passes through the cornea and is focused by the lens onto the retina. The macula (Latin for “spot”) is a feature of human and most nonhuman primate retinas and lies in the central visual axis. The fovea (Latin for “pit”) is a small region at the center of the macula adapted for high-acuity vision. Two vascular networks—one in the neural retina and the other in the choroid—support the high metabolic demands of the retina. Rod and cone photoreceptors rely principally on the choroidal blood supply. Metabolites destined for the rods and cones are shuttled from the choroid to the photoreceptors by the retinal pigment epithelium. Neuronal impulses generated in the retina are conveyed to the brain by the optic nerve. (Center) Fundus photograph of the retina of a healthy individual. Using an ophthalmoscope, the retina can be evaluated as part of a routine eye exam. The optic nerve, macula, and retinal blood vessels provide ophthalmologists with clues about patients’ ocular health. (Right) Confocal microscopy image of a human retina labeled with fluorescent probes to show the close apposition of photoreceptors, retinal pigment epithelium, Bruch’s membrane, and choroidal blood vessels. Cell nuclei in the outer nuclear layer of photoreceptors are red, photoreceptor outer segments are green, and structures containing high concentrations of filamentous actin (cell–cell junctions and vessel walls) are blue. The inner segments of photoreceptors contain metabolic components, including numerous mitochondria. (b) AMD pathology. (Left,center) Fundus photographs depicting two distinct pathological features of AMD. The photograph on the left shows the characteristic accumulation of drusen, which appear as yellow splotches and flecks within the macula. The photograph in the center shows the unmistakable evidence of hemorrhage beneath the retina resulting from the pathological process of choroidal neovascularization (CNV). The decline in visual function associated with CNV hemorrhage is often rapid and irreversible. (Right) Micrograph showing pathological changes characteristic of AMD, outside the zone of geographic atrophy (GA). Layers of cells and extracellular lesions have been pseudocolored to highlight the extensive disorganization that has occurred at the interfaces between the photoreceptors, the retinal pigment epithelium, Bruch’s membrane, and the choroid. The outer plexiform layer includes synapses of photoreceptors with neurons in the inner retina. Lipid-rich deposits accumulate between the retinal pigment epithelium and Bruch’s membrane (dull yellow), and between the retinal pigment epithelium and photoreceptors (bright yellow). These deposits compromise the delivery of metabolites from the choroid to the photoreceptors and may initiate or exacerbate inflammatory processes, resulting in retinal pigment epithelium and photoreceptor cell death. Adapted in part from Reference 104.