Apoptosis in surgically excised choroidal neovascular membranes in age-related macular degeneration.
BACKGROUND
Choroidal neovascular membranes (CNVMs) in age-related macular degeneration show progressive histologic changes from active, cellular, highly vascularized membranes to inactive paucicellular scars. The purpose of this study was to determine whether apoptosis was involved in the evolution of these changes, what cell types are involved, and whether there was an association with the Fas antigen (Fas or CD95) and Fas ligand (FasL).


METHODS
Serial frozen sections from 10 surgically excised CNVMs were stained by the TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine 5-triphosphate nick-end labeling) method for detection of DNA strand breaks and by propidium iodide staining for morphologic detection of apoptosis. Immunoperoxidase staining was used for detection of Fas, FasL, and cell-type specific antigens.


RESULTS
Highly vascularized membranes contained cells with TUNEL-positive nuclei, particularly in the regions of neovascularization, while fibrotic membranes showed few, if any, TUNEL-positive cells. Many of the TUNEL-positive cells were stromal retinal pigment epithelial cells, although smaller numbers were identified as endothelial cells and macrophages. Confocal microscopy of propidium idoide-stained sections confirmed the presence of apoptotic nuclei. The extent of Fas antigen expression correlated with extent of apoptosis. FasL expression was found in all specimens but was most intense in the highly vascularized membranes.


CONCLUSIONS
Highly vascularized CNVMs related to age-related macular degeneration show apoptosis in stromal retinal pigment epithelial cells, endothelial cells, and occasional macrophages. Apoptosis is associated with prominent Fas and FasL expression.
Hinton
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DR
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
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Lopez
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PF
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002829:Choroid / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000473:pathology; D008268:Macular Degeneration / Q000150:complications*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008566:Membranes / Q000098:blood supply; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004253:DNA Nucleotidylexotransferase