BACKGROUND: The process of identifying molecules that regulate angiogenesis is critical to the success of candidate therapies for ocular neovascular disease. The purpose of the study was to determine the pattern of expression for integrins and their colocalization with endothelium in membranes from proliferative diabetic retinopathy (PDR). METHODS: Clinically categorized membranes were collected from vitreoretinal surgery. A double immunohistochemical staining procedure was used to identify the presence and colocalization of integrins and endothelium. Five integrins were examined. RESULTS: Endothelial markers were robust in all 4 active-stage PDR membranes but absent in the fibrotic-stage PDR membrane. The expression of alpha;vbeta3 and beta3 integrins on endothelial cells was observed with low to moderate intensity. The expression of alpha;1beta1 and alpha;2beta1 was moderate but was not colocalized with endothelial cells in active-stage PDR membranes. Integrin alpha;vbeta5 was not evident in any of the samples used in this study. INTERPRETATION: The results suggest an essential role of integrins alpha;vbeta3 and beta3 in the pathogenesis of PDR. It is suggested that alpha;vbeta3 and beta3 are preferred candidate targets for therapeutic development.
BACKGROUND: The process of identifying molecules that regulate angiogenesis is critical to the success of candidate therapies for ocular neovascular disease. The purpose of the study was to determine the pattern of expression for integrins and their colocalization with endothelium in membranes from proliferative diabetic retinopathy (PDR). METHODS: Clinically categorized membranes were collected from vitreoretinal surgery. A double immunohistochemical staining procedure was used to identify the presence and colocalization of integrins and endothelium. Five integrins were examined. RESULTS: Endothelial markers were robust in all 4 active-stage PDR membranes but absent in the fibrotic-stage PDR membrane. The expression of alpha;vbeta3 and beta3 integrins on endothelial cells was observed with low to moderate intensity. The expression of alpha;1beta1 and alpha;2beta1 was moderate but was not colocalized with endothelial cells in active-stage PDR membranes. Integrin alpha;vbeta5 was not evident in any of the samples used in this study. INTERPRETATION: The results suggest an essential role of integrins alpha;vbeta3 and beta3 in the pathogenesis of PDR. It is suggested that alpha;vbeta3 and beta3 are preferred candidate targets for therapeutic development.
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