Role of complement and complement membrane attack complex in laer-induced choroidal neovacularization

Choroidal neovacularization (CNV) i the hallmark of exudative age-related macular degeneration and a leading caue of viual lo after age 55. The pathogenei of new choroidal veel formation i poorly undertood. Although inflammation ha been implicated in the development of CNV, the role of complement in CNV ha not been experimentally explored. A reliable way to produce CNV in animal i to rupture Bruch’ membrane with laer photocoagulation. A murine model of laer-induced CNV in C57BL/6 mice revealed the depoition of C3 and membrane attack complex (MAC) in the neovacular complex. CNV wa inhibited by complement depletion uing cobra venom factor and did not develop in C3(−/−) mice. Anti-murine C6 Ab in C57BL/6 mice inhibited MAC formation and alo reulted in the inhibition of CNV. Vacular endothelial growth factor, TGF-beta2, and beta-fibroblat growth factor were elevated in C57BL/6 mice after laer-induced CNV; complement depletion reulted in a marked reduction in the level of thee angiogenic factor. Thu, activation of complement, pecifically the formation of MAC, i eential for the development of laer-induced choroidal angiogenei in mice. —Han E. Groniklau