Abstract
Abstract: :
Purpose: To examine the association of microvascular changes in the choriocapillaris with age–related maculopathy (ARM) and complement complex accumulation in human donor eyes. Methods: Macular choriocapillaris lumen areas and numbers of "ghost" vessels per viable capillary were determined from electron micrographs obtained from 28 donor eyes. Donor eyes were classified as controls (age > 60, no evidence of macular disease; n = 14) or ARM (age > 58, with macular drusen and/or pigment changes, but with no evidence of advanced disease; n = 14). The choriocapillaris lumen area per unit length was measured in a masked fashion, and results were analyzed as a function of presence of macular disease and degree of terminal complement complex deposition as assessed immunohistochemically. In a separate experiment, choriocapillaris density was compared with the complement sC5b–9 levels measured in 10 eyes by ELISA (controls, n=4; ARM, n=3; advanced AMD, n=3). Results: A significant decrease in the density of the choriocapillaris was observed in ARM. In controls, the mean capillary area was 4.80 µm2 per µm of Bruch’s membrane. In ARM, the mean capillary density was 3.68µm2 per µm of Bruch’s membrane; this value is significantly lower than measured in controls (p=0.014). Decreased capillary density was also observed in association with increased complement accumulation, particularly between eyes with no histochemically detectable C5b–9 and eyes with either moderate or intense C5b–9 labeling (p=0.015). The degree of complement complex accumulation and AMD status had independent effects on the choriocapillaris density (interaction p value =0.98). The odds–ratio is 8.0 for ARM with intense C5b–9 labeling vs. no detectable level. In ELISA experiments, a weak association between decreased capillary density and increased C5b–9 was observed (r=0.39). Conclusions: Choriocapillaris density is decreased in ARM and in association with complement accumulation. Injury to the choriocapillaris—potentially induced by complement attack—may contribute to the progression of early AMD to more advanced disease.
Keywords: age–related macular degeneration • choroid • pathobiology