CD-95 EXPRESSION IN TRAUMATIC PROLIFERATIVE VITREORETINOPATHY - A TARGET FOR THE INDUCTION OF APOPTOSIS

Apoptotic cell death is a central mechanism underlying growth regulati on in normal and pathologic neoplastic and nonneoplastic tissue format ion. Apoptosis has also been detected in traction membranes of patient s with proliferative vitreoretinopathy (PVR). Herein we report that CD 95 (Fas/APO-1), the cell-surface receptor for a potent proapoptotic c ytokine, the CD 95 ligand, is expressed in traction membranes of patie nts with traumatic PVR. Retinal pigment epithelial (RPE) cells, which are thought to contribute to traction membrane formation, express CD 9 5 in vitro. However, these cells are resistant to CD 95 antibody-induc ed apoptosis, presumably because they synthesize cytoprotective protei ns, which interfere with the CD 95-dependent killing cascade. Coexposu re to inhibitors of RNA of protein synthesis sensitizes human RPE cell s for CD 95-mediated apoptosis, In contrast, these agents have little effect on the resistance of these cells to tumor necrosis factor-alpha (TNF-alpha). Preexposure to TNF-alpha augments CD95-mediated killing but not its own toxicity in the presence of inhibitors of RNA and prot ein synthesis. Preexposure to cycloheximide does not abrogate CD 95-me diated apoptosis, suggesting that labile, short-lived proteins do not mediate the cytotoxic effects of CD 95 antibodies. Taken together, our data indicate that immune-mediated CD 95-dependent killing of prolife rating cells in vitreoretinal traction membranes might occur in vivo a nd could possibly be enhanced using novel approaches of immunopharmaco therapy.