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E.L. Fletcher, S. Ninkovic, L. Foster, D. Jones, T. De Gooyer, A. Stitt, J.L. Wilkinson–Berka; Progressive vascular and neurochemical changes in retinae of diabetic (mRen–2)27 rats. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3240.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent studies have implicated the renin–angiotensin system in vascular changes during diabetes. In addition to vascular abnormalities, there may be alterations in neuronal and glial function. The aim of this project was to characterize the vascular and neuroglial changes in the (mRen–2)27 rat model of diabetes. Methods: Sprague–Dawley and hypertensive (mRen–2)27 transgenic rats were rendered diabetic by an intravenous injection of STZ (50mg/kg). Control rats received injections of citrate buffer alone. Following 4, 10 or 20 weeks of diabetes, animals were sacrificed by anaesthetic overdose, their eyes removed and either processed for an examination of the vasculature or neurochemistry. Acellular capillaries were examined following digestion of the neural retina with trypsin. Retinal vascular leakage was estimated using the Evan’s blue technique. Amino acid immunocytochemistry was performed using antisera directed against glutamate, GABA, glycine, aspartate, alanine, glutamine, arginine, taurine, ornithine and glutamine synthetase (kindly donated by Dr RE Marc). Changes in amino acid labelling in subpopulations of neurons and Müller cells were analysed by image analysis using NIH Image. Results: Vascular abnormalities were observed following 10 weeks of diabetes; at this time there was an increase in acellular capillaries in the mid and peripheral retina, which became more marked at 20 weeks (periphery non–diabetic Ren–2, 0.70+0.007; periphery diabetic Ren–2, 1.91+0.44). This was accompanied by venous beading and microaneurysms. In all groups, vascular leakage was unchanged with diabetes at 4 weeks. By 10 weeks of diabetes, retinal vascular leakage had increased by approximately 2 fold in Ren–2 rats (non–diabetic Ren–2, 6.07+0.89; diabetic Ren–2, 13.06+1.44 ul plasma /gm retinal weight/hr). Significant changes in amino acid neurochemistry were observed in the diabetic (mRen–2)27 rat retina. In particular Müller cells displayed an increase in GABA and arginine immunoreactivity and no change in glutamate or glutamine. There were increases in labelling to aspartate, alanine and ornithine in subpopulations of amacrine cells in the diabetic (mRen–2) 27 rat compared with controls. Conclusions: These data suggest that there are marked abnormalities in the vasculature of the diabetic (mRen–2)27 rat retina accompanined by neurochemical changes in neurons and glia.
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