Vasoregression is also the hallmark of diabetic retinopathy in both, humans, and animal models. Changes in pericyte coverage of microvessels, in endothelial cells and an increasing number of acellular capillaries of TGR retinas are qualitatively similar to those in experimental diabetic retinopathy. Pericyte loss is an early and archetypical feature of diabetic retinopathy. In contrast to the diabetic model, in which pericyte loss appears to be causally linked to glucose-induced changes in angiopoietin-2 expression,SP600125 the mechanism of pericyte loss in the TGR model remains yet to be determined. Neither glial activation which occurs prior to pericyte loss in the TGR model nor endothelial cell loss which starts in parallel with pericyte loss might be responsible, since key factors determining pericyte recruitment are not altered in TGR model. Angiopoietin-1 is produced by glial cells, and PDGF-B by endothelial cells. Neither of which are changed in the TGR model. Pericytes act as survival factors for established capillaries, and their loss may therefore be relevant in vasoregression. However, despite the similar degree of pericyte dropout in the TGR compared to the diabetic model,Sorafenib the degree of acellular capillaries differs substantially between the two models. Therefore, pericyte loss is unlikely to explain the enormous level of vasoregression in the TGR. The final cause for the exorbitant demise of vessels remains unclear, but it is obvious that the disturbed integrity of the neurovascular unit is responsible. One factor relevant for proper retinal vessel function and neurovascular integrity, i.e. VEGF, does not respond to the neuronal damage in the TGR model. In contrast to other models of retinal degeneration such as the rho-/-mouse in which VEGF is reduced, we did not find hypoxia in the TGR model, and consistent with the lack of hypoxia, VEGF was not regulated with progressive vascular regression. The absence of VEGF regulation is one of the discrepancies between the TGR and the diabetic retinopathy model in which VEGF is induced by hyperglycemia and the resultant increase in oxidative stress and advanced glycation endproducts formation.