Diabetic Retinopathy and Neuropathy

Abstract

This is the seventh in a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004. Holger Gerhardt (Goteborg, Sweden) discussed pericytes and vascular stability in the diabetic retina, noting that these cells cover most of the endothelium and are present during the development of normal new blood vessels, while proliferative retinopathy classically shows “pericyte drop out” as an early pathological marker. It has been hypothesized that endothelial dysfunction leads to capillary occlusion and regression, causing ischemia, to which neovascularization with subsequent proliferative retinopathy is a response. In this schema, pericyte drop out may occur either before or after the stage of endothelial dysfunction. A number of markers can be used for characterizing pericytes. Mice that do not express platelet-derived growth factor (PDGF)-β have severe diffuse bleeding and die early in the neonatal period. There is diffuse pericyte loss in these mice, suggesting PDGF-β to be an important growth factor for the cells. An endothelium-specific PDGF-β knockout displays a variety of phenotypes with variable degrees of pericyte loss, with areas of pericyte-covered vessels and areas lacking pericytes and with severe retinopathy localized to the areas lacking pericytes. Gerhardt suggested that pericyte drop out is therefore sufficient to cause capillary occlusion and regression, leading to retinal ischemia. Why, though, he asked, is there a proliferative response rather than normal development of well-behaved new vessels repairing the region of ischemia, and how does retinal normal vascular development differ from that seen in neovascularization? The normal advancing vascular sprout extends “tip cells,” which appear to guide the development of the vasculature, following paths produced by astrocytes, which produce vascular endothelial growth factor (VEGF)-α in areas of hypoxia, with astrocyte VEGF-α downregulated after it becomes covered by new vessels. In the developing retina, the VEGF receptor (R)2 …