Premium
Endothelium‐specific platelet‐derived growth factor‐B ablation mimics diabetic retinopathy
Author(s) -
Enge Maria,
Bjarnegård Mattias,
Gerhardt Holger,
Gustafsson Erika,
Kalén Mattias,
Asker Noomi,
Hammes HansPeter,
Shani Moshe,
Fässler Reinhardt,
Betsholtz Christer
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf418
Subject(s) - biology , endothelium , ablation , diabetic retinopathy , platelet , growth factor , retinopathy , medicine , diabetes mellitus , endocrinology , immunology , biochemistry , receptor
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.