CD95 (FAS APO-1) ANTIBODY-MEDIATED APOPTOSIS OF HUMAN RETINAL-PIGMENTEPITHELIAL-CELLS/

CD95 (Fas/APO-1) is a cytokine receptor protein that signals apoptosis . Here we report that human retinal pigment epithelial cells express C D95 but are rather resistant to agonistic CD95 antibodies. Resistance to CD95 antibodies is overcome by preexposure to the cytokines, tumor necrosis factor-alpha or interferon-gamma, or by coexposure to CD95 an tibodies and inhibitors of RNA or protein synthesis. The cells are res istant to tumor necrosis factor-alpha even in the presence of cyclohex imide and only moderately sensitized to tumor necrosis factor-alpha-me diated toxicity by coexposure to actinomycin D. CD95-mediated apoptosi s is inhibited by dexamethasone both after cytokine sensitization and upon coexposure to CD95 antibodies and actinomycin D or cycloheximide. Induction of apoptosis via CD95 may be involved in the regulation of retinal pigment epithelial proliferation at the vitreoretinal interfac e. (C) 1995 Academic Press, Inc.