APOPTOSIS IN SURGICALLY EXCISED CHOROIDAL NEOVASCULAR MEMBRANES IN AGE-RELATED MACULAR DEGENERATION

Background: Choroidal neovascular membranes (CNVMs) in age-related mac ular degeneration show progressive histologic changes from active, cel lular, highly vascularized membranes to inactive paucicellular scars. The purpose of this study was to determine whether apoptosis was invol ved in the evolution of these changes, what cell types are involved, a nd whether there was an association with the Fas antigen (Fas or CD95) and Fas ligand (FasL). Methods: Serial frozen sections from 10 surgic ally excised CNVMs were stained by the TUNEL (terminal deoxynucleotidy l transferase-mediated biotin-deoxyuridine 5-triphosphate nick-end lab eling) method for detection of DNA strand breaks and by propidium iodi de staining for morphologic detection of apoptosis. Immunoperoxidase s taining was used for detection of Fas, FasL, and cell-type specific an tigens. Results: Highly vascularized membranes contained cells with TU NEL-positive nuclei, particularly in the regions of neovascularization , while fibrotic membranes showed few, if any, TUNEL-positive cells. M any of the TUNEL-positive cells were stromal retinal pigment epithelia l cells, although smaller numbers were identified as endothelial cells and macrophages. Confocal microscopy of propidium idoide-stained sect ions confirmed the presence of apoptotic nuclei. The extent of Fas ant igen expression correlated with extent of apoptosis. FasL expression w as found in all specimens but was most intense in the highly vasculari zed membranes. Conclusions: Highly vascularized CNVMs related to age-r elated macular degeneration show apoptosis in stromal retinal pigment epithelial cells, endothelial cells, and occasional macrophages. Apopt osis is associated with prominent Fas and FasL expression.