Purpose. Subretinal neovascular (SRN) membranes in age-related macular degeneration (ARMD) show progressive histologic changes. Membranes are initially cellular and highly vascularized while older membranes may become paucicellular and fibrotic. The purpose of this study was to determine whether the mechanism of reduction of cellularity in these membranes was by apoptosis. Methods. Frozen sections from six surgically-excised ARMD-related SRN membranes were stained by the TUNEL method for evidence of apoptosis. Adjacent sections were then double stained with TUNEL and cell-type specific antibodies to determine which cell types were undergoing apoptosis. Results. Highly vascularized, cellular membranes showed many TUNEL positive nuclei in the stroma particularly in the regions of prominent neovascularization, while paucicellular fibrotic membranes showed few if any TUNEL positive cells. Double staining revealed that many of the TUNEL positive cells in the stroma were also cytokeratin-18 positive indicating that they represent transdifferentiated RPE. Smaller numbers of endothelial cells (Factor VIII) and macrophages (CD68 positive) were also TUNEL positive. Conclusions. Highly vascularized SRN membranes surgically excised from ARMD patients show prominent apoptosis in transdifferentiated RPE, endothelial cells and occasional macrophages. The resolution of these membranes by apoptois is similar to that found in granulation tissue and provides support for the idea that SRN has many features of a stereotyped wound healing response.
