Figure 3. The retina in AMD.

(A) In neovascular AMD, it is hypothesized that choriocapillaris atrophy leads to ischemia of the RPE, which triggers VEGF secretion and the growth of abnormal choroidal blood vessels. These vessels breach BM and grow in the sub-RPE or subretinal space, causing accumulation of subretinal and intraretinal fluid. (B) In atrophic AMD, it is thought that some primary insult leads to RPE degeneration, which causes choriocapillaris atrophy due to the role of the RPE in supporting choriocapillaris function. As the RPE degenerates, the overlying photoreceptors die. In both types of AMD, there is choriocapillaris atrophy and RPE degeneration, though the sequence of events in each disease may be different. In terms of complement activity in AMD, increased concentrations of C3, C3a, Bb, FB, and FD have been detected within BM and choriocapillaris of human donor eyes with AMD (denoted by asterisks) (100). Cadaver studies have found MAC deposition in the RPE and choriocapillaris of patients with the Y402H polymorphism in CFH regardless of whether AMD changes are present (88, 89). The Y402H polymorphism is believed to contribute to AMD pathogenesis primarily through its effect on FHL-1, as FHL-1 is the major complement regulator of BM (83, 84).