Fas ligand (CD95 ligand) controls angiogenesis beneath the retina

A principal cause of blindness is subretinal neovascularization associated with age-related macular degeneration. Excised neovascular membranes from p atients with age-related macular degeneration demonstrated a pattern of Fas (+) new vessels in the center of the vascular complex, surrounded by FasL() retinal pigment epithelial cells. In a murine model, Fas (CD95)-deficient (lpr) and Fast-defective (gld) mice had a significantly increased incidenc e of neovascularization compared with normal mice. Furthermore, in gld mice there is massive subretinal neovascularization with uncontrolled growth of vessels. We found that cultured choroidal endothelial cells were induced t o undergo apoptosis by retinal pigment epithelial cells through a Fas-FasL interaction. In addition, antibody against Fas prevented vascular tube form ation of choroidal endothelial cells derived from the eye in a three-dimens ional in vitro assay. Thus, Fast expressed on retinal pigment epithelial ce lls may control the growth and development of new subretinal vessels that c an damage vision.