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P. Bu, X. Zhang, A.J. Emerick, J.I. Perlman, E.B. Stubbs, Jr.; Neurotransmitter Distribution in Experimental Diabetic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3232.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Microangiopathy is a pathologic hallmark of diabetic retinopathy, a major sight–threatening disease in developed countries. However, a number of observations suggest that non–vascular changes, including glutamate excitotoxicity, may also contribute to retinal dysfunction in affected patients. It has been proposed that a breakdown of the blood–retinal barrier, which occurs early in diabetes, may elevate retinal glutamate levels leading to retinal injury. In this study, the effects of sustained hyperglycemia on retinal function, neurotransmitter distribution and vitreal–retinal glutamate and aspartate content were determined using an established animal model of type 1 diabetes mellitus. Methods: Non–fasted male Sprague–Dawley rats (265g) received either a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg body weight) or an equal volume of vehicle (citrate buffer, pH 4.5). Blood glucose was determined weekly using a commercial glucometer. At 8 weeks following treatment, rats were dark–adapted x 2h, anesthetized, pupils dilated and electroretinogram (ERG) responses recorded. The distribution of retinal neurotransmitters was determined by immunogold immuno–histochemistry with silver intensification. Vitreal–retinal glutamate and aspartate content was quantitated by HPLC. Results:Rats treated with a single injection of STZ developed and sustained elevated levels of blood glucose (506 + 28 mg %, n=5; p<0.0001) compared to vehicle–treated control (94 + 3 mg %, n=4). At 8–weeks following STZ–treatment, ERG a–wave and b–wave amplitudes were significantly (p< 0.05) reduced while implicit times were lengthened. No significant changes in retinal morphology, in the distribution of retinal neurotransmitters glutamate, aspartate, glutamine or GABA, or changes in the vitreal–retinal content of glutamate or aspartate were observed in STZ–treated rats compared to vehicle–treated controls. Conclusion: Sustained (8–10 weeks) hyperglycemic insult in vivo to Sprague–Dawley male rats elicited early visual deficits as quantitated by ERG. Altered retinal function was not associated with changes in retinal morphology, neurotransmitter distribution or with changes in vitreal–retinal glutamate or aspartate content. These results suggest that early pathological changes in diabetic retinopathy proceed by mechanisms independent of glutamate excitotoxicity.
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