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Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy

Item Type:Article
Title:Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy
Creators Name:Enge, M. and Bjarnegård, M. and Gerhardt, H. and Gustafsson, E. and Kalén, M. and Asker, N. and Hammes, H.-P. and Shani, M. and Fässler, R. and Betsholtz, C.
Abstract:Loss of pericytes from the capillary wall is a hallmark of diabetic retinopathy, however, the pathogenic significance of this phenomenon is unclear. In previous mouse gene knockout models leading to pericyte deficiency, prenatal lethality has so far precluded analysis of postnatal consequences in the retina. We now report that endothelium-restricted ablation of platelet-derived growth factor-B generates viable mice with extensive inter- and intra-individual variation in the density of pericytes throughout the CNS. We found a strong inverse correlation between pericyte density and the formation of a range of retinal microvascular abnormalities strongly reminiscent of those seen in diabetic humans. Proliferative retinopathy invariably developed when pericyte density was <50% of normal. Our data suggest that a reduction of the pericyte density is sufficient to cause retinopathy in mice, implying that pericyte loss may also be a causal pathogenic event in human diabetic retinopathy.
Keywords:Cre-loxP System, Diabetes, Pericytes, Platelet-Derived Growth Factor, Retinopathy, Animals, Mice
Source:EMBO Journal
Publisher:Oxford University Press
Page Range:4307-4316
Date:15 August 2002
Official Publication:https://doi.org/10.1093/emboj/cdf418
PubMed:View item in PubMed

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