International Linkages
Project 7
Neuronal and glial damage in a transgenic model of diabetic retinopathyDiabetic retinopathy is the leading cause of new cases of legal blindness between 20 and 74 years of age being a chronic disorder that eventually develops, to some degree, in nearly all patients with diabetes mellitus (1). The condition is characterised by a number of readily identifiable progressive changes within the retinal vasculature which have been extensively described both clinically and experimentally. Changes in the vasculature include increased retinal vascular permeability, microaneurysms, venous tortuosity, capillary non-perfusion and dropout, endothelial and pericyte loss and neovascularisation (2). In addition, there is ample evidence that non-vascular damage also occurs. For example, neuronal loss has been reported and retinal glia (Müller cells) respond breaching the walls of damaged capillaries and block the lumen, thus presumably contributing to capillary non-perfusion and dropout (3,4). Recently, we generated a number of transgenic mice using vascular endothelial growth factor (VEGF) linked to an opsin promoter thus targeting transgene expression to the eye. One line (trVEGF029) was of particular interest because, despite being on a normoglycaemic background, it clearly displayed many of the vascular changes which occur in diabetic retinopathy (5). While we have now characterized many of the vascular changes, we know little of the status of neurons and Müller cells. This project will characterize the transgenic retina further by determining the extent of neuronal loss and Müller cell damage. Eyes will be sectioned and examined immunohistochemically using markers specific (eg Tuj-1 for retinal ganglion cells; glutamine synthase for Müller cells). Evidence for invasion of capillaries by Müller cells will also be sought. The project will have implications for understanding mechanisms of cell damage in diabetic retinopathy with a long term goal of improving therapies.
  
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