Related Experiment Videos
Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy
Maria Enge1, Mattias Bjarnegård, Holger Gerhardt
1Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden.
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.
Insights
Pericyte loss from retinal capillaries is linked to diabetic retinopathy. This study shows reduced pericyte density in mice causes retinopathy, suggesting pericyte loss is a key factor in human diabetic eye disease.
Area of Science:
- Ophthalmology
- Vascular Biology
- Diabetic Complications
Background:
- Loss of pericytes from retinal capillaries is a hallmark of diabetic retinopathy.
- The pathogenic role of pericyte loss in diabetic retinopathy remains unclear.
- Previous studies were limited by prenatal lethality in mouse models of pericyte deficiency.
Purpose of the Study:
- To investigate the consequences of pericyte deficiency on retinal microvasculature.
- To determine if reduced pericyte density is sufficient to cause retinopathy.
- To establish a viable mouse model for studying pericyte loss in the retina.
Main Methods:
- Endothelium-restricted ablation of platelet-derived growth factor-B (PDGF-B) in mice.
- Analysis of pericyte density and retinal microvascular abnormalities.
- Correlation of pericyte density with retinopathy development.
Main Results:
- Generated viable mice with variable pericyte densities in the central nervous system (CNS).
- Found a strong inverse correlation between pericyte density and retinal microvascular abnormalities.
- Pro-liferative retinopathy developed when pericyte density fell below 50% of normal.
Conclusions:
- Reduced pericyte density is sufficient to induce retinopathy in mice.
- Pericyte loss may be a causal pathogenic event in human diabetic retinopathy.
- This model allows for further investigation into the mechanisms of diabetic retinopathy.