Pericytes and the Pathogenesis of Diabetic Retinopathy
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- 1 October 2002
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 51 (10), 3107-3112
- https://doi.org/10.2337/diabetes.51.10.3107
Abstract
Pericytes provide vascular stability and control endothelial proliferation. Pericyte loss, microaneurysms, and acellular capillaries are characteristic for the diabetic retina. Platelet-derived growth factor (PDGF)-B is involved in pericyte recruitment, and brain capillaries of mice with a genetic ablation of PDGF-B show pericyte loss and microaneurysms. We investigated the role of capillary coverage with pericytes in early diabetic retinopathy and the contribution to proliferative retinopathy using mice with a single functional allele of PDGF-B (PDGF-B+/− mice). As assessed by quantitative morphometry of retinal digest preparations, pericyte numbers in nondiabetic PDGF-B+/− mice were reduced by 30% compared with wild-type mice, together with a small but significant increase in acellular capillaries. Pericyte numbers were reduced by 40% in diabetic wild-type mice compared with nondiabetic wild-type controls. Pericyte numbers were decreased by 50% in diabetic PDGF-B+/− mice compared with nondiabetic wild-type littermates, and the incidence of acellular capillaries was increased 3.5-fold when compared with nondiabetic PDGF-B+/− mice. To investigate the effect of pericyte loss in the context of ongoing angiogenesis, we subjected mice to hypoxia-induced proliferative retinopathy. As a result, PDGF-B+/− mice developed twice as many new blood vessels as their wild-type littermates. We conclude that retinal capillary coverage with pericytes is crucial for the survival of endothelial cells, particularly under stress conditions such as diabetes. At high vascular endothelial growth factor levels, such as those in the retinopathy of prematurity model, pericyte deficiency leads to reduced inhibition of endothelial proliferation in vivo.Keywords
This publication has 31 references indexed in Scilit:
- Ras‐dependent and ‐independent regulation of reactive oxygen species by mitogenic growth factors and TGF‐β1The FASEB Journal, 2000
- Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawalJCI Insight, 1999
- PDGF, TGF-β, and Heterotypic Cell–Cell Interactions Mediate Endothelial Cell–induced Recruitment of 10T1/2 Cells and Their Differentiation to a Smooth Muscle FateThe Journal of cell biology, 1998
- Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient MiceScience, 1997
- Role of tissue factor in embryonic blood vessel developmentNature, 1996
- Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.JCI Insight, 1996
- Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formationNature, 1995
- Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.Genes & Development, 1994
- mRNA expression of growth factors in glomeruli from diabetic ratsDiabetes, 1993
- Pathogenesis of diabetic retinopathyDiabetes, 1989