Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy.
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.
Enge
Maria
M
Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden.
Bjarnegård
Mattias
M
Gerhardt
Holger
H
Gustafsson
Erika
E
Kalén
Mattias
M
Asker
Noomi
N
Hammes
Hans-Peter
HP
Shani
Moshe
M
Fässler
Reinhardt
R
Betsholtz
Christer
C
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D017353:Gene Deletion; D018390:Gene Targeting; D051379:Mice; D008822:Mice, Transgenic; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D020574:Proto-Oncogene Proteins c-sis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology
D020574:Proto-Oncogene Proteins c-sis