A principal cause of blindness is subretinal neovascularization associated
with age-related macular degeneration. Excised neovascular membranes from
patients 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 FasL-defective (gld) mice had
a significantly increased incidence 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 to undergo apoptosis by retinal pigment epithelial cells
through a Fas−FasL interaction. In addition, antibody against Fas prevented
vascular tube formation of choroidal endothelial cells derived from the eye
in a three-dimensional in vitro assay. Thus, FasL expressed on retinal
pigment epithelial cells may control the growth and development of new subretinal
vessels that can damage vision.
