Fas ligand (CD95 ligand) controls angiogenesis beneath the retina

Henry J. Kaplan, Marc A. Leibole, Tongalp Tezel, Thomas A. Ferguson

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)292-297
Number of pages6
JournalNature medicine
Volume5
Issue number3
DOIs
StatePublished - Mar 22 1999

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