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Pericytes and the pathogenesis of diabetic retinopathy
Hans-Peter Hammes1, Jihong Lin, Oliver Renner
1Fifth Medical Clinic, Medical Faculty of the University of Heidelberg, Mannheim, Germany. hans-peter.hammes@med5.ma.uni-heidelberg.de
Insights
Pericyte loss exacerbates diabetic retinopathy by increasing acellular capillaries and neovascularization. Maintaining pericyte coverage is vital for retinal vascular stability, especially under diabetic stress.
Area of Science:
- Ophthalmology
- Vascular Biology
- Diabetic Complications
Background:
- Pericytes stabilize blood vessels and regulate endothelial cell growth.
- Diabetic retinopathy is characterized by pericyte loss, microaneurysms, and acellular capillaries.
- Platelet-derived growth factor (PDGF)-B is crucial for pericyte recruitment.
Purpose of the Study:
- To investigate the role of pericyte coverage in early diabetic retinopathy.
- To assess the contribution of pericyte deficiency to proliferative retinopathy.
- To evaluate the impact of reduced PDGF-B signaling on retinal vascular integrity.
Main Methods:
- Quantitative morphometry of retinal digest preparations in PDGF-B(+/-) mice and wild-type littermates.
- Induction of hypoxia-induced proliferative retinopathy.
- Assessment of pericyte numbers and acellular capillary incidence.
Main Results:
- PDGF-B(+/-) mice exhibited a 30% reduction in pericytes and increased acellular capillaries.
- Diabetic wild-type mice showed a 40% decrease in pericytes.
- Diabetic PDGF-B(+/-) mice had a 50% pericyte reduction and a 3.5-fold increase in acellular capillaries.
- PDGF-B(+/-) mice developed twice as many new blood vessels under hypoxic conditions.
Conclusions:
- Retinal pericyte coverage is critical for endothelial cell survival, especially in diabetes.
- Pericyte deficiency exacerbates vascular pathology in diabetic retinopathy.
- Reduced pericyte coverage impairs the inhibition of endothelial proliferation under stress.
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.