Cerebrum Spring 2021

the waste of photoreceptors, that collect in the extracellular space. Because they are unlike anything normally present in the retina, the deposits are easily mistaken for invading bacteria or viruses, activating the complement cascade. (We know this because analysis of drusen has found fragments of proteins seen only in tissues in which such activation has occurred.) Activating the complement system results in bystander damage, particularly to blood vessels that supply the photoreceptors. To explain things, I showed my patient a schematic picture of a retina with AMD (Figure 1). Damage to blood vessels reduces delivery of oxygen and nutrients to photoreceptors and RPE cells causing gradually progressive damage referred to as “dry” AMD. For a while the photoreceptors can survive the lack of oxygen and nutrients but function sub-optimally, making it difficult to read without bright illumination. But over time, they and their supporting RPE cells begin to die, causing blank spots

proteins, RNA, and DNA, to the extracellular environment, in patterns that mimic those of foreign invaders. In a patient with AMD, normal aging is exacerbated by genetic differences that create abnormal deposits under the retina’s photoreceptors and/or retinal pigmented epithelial (RPE) cells. (Photoreceptors are the cells that respond to light and convert it into electrical signals, beginning the process by which the brain constructs images of the environment. RPE cells are a support system that helps to nourish photoreceptors, dispose of their waste, and provide a barrier between them and underlying blood vessels.) These deposits, which are the aforementioned yellow spots that occur under the retina and were seen during the examination of the patient, are referred to as drusen. They develop gradually as patients with AMD age, which is why AMD most often occurs in seniors. The deposits contain aggregates of diverse proteins and other materials, particularly

FIGURE 1. Schematic of the pathogenesis of age-related macular degeneration

Cystoid Spaces

Nerve Fiber Layer

Geographic Atrophy

Ganglion Cell Layer

Inner Plexiform Layer Inner Nucleur Layer

Outer Plexiform Layer Out Nucleur Layer Inner Segment

Outer Segment Retinal Pigment Epithelium Bruch's Membrane Choriocapillaris Choroidal Vessels

Complement Activation Dropout of Choriocapillaries

Choroidal Neovascularization

Activation of the complement system causes damage to the blood vessels that supply oxygen and nutrients to the retinal pigment epithelium and photoreceptors. Severe damage causes these cells to die, resulting in advanced dry AMD (called geographic atrophy). Sometimes the damaged photoreceptors and retinal pigment epithelial cells produce vascular endothelial growth factor (VEGF), which causes new blood vessels to grow under the retina. This can keep the cells alive but, at the same time, leak fluid into the retina, resulting in pockets of fluid (cystoid spaces) that reduce vision. This is called wet AMD. Vision can be improved and maintained by injections that block VEGF.



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