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Kavita R. Hegde, Shambhu D. Varma; Preventive Effect Of Topical Ethyl Pyruvate Against Diabetes-induced Damage To The Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2423.
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Oxidative stress is considered to be a highly significant factor in the pathogenesis of diabetic retinopathy-a major cause of vision impairment and blindness. Excessive generation of oxygen free radicals due to high glucose is known to have deleterious effects on tissue structure and function by causing oxidative modification of lipids, protein and nucleic acids. It is hypothesized that pyruvate, a potent free radical scavenger, will prevent such stress to the retina in diabetic mice. This hypothesis is based on our previous studies demonstrating the protective effect of pyruvate against oxidative damage to the retina in vitro, and to lens in vivo-evident by cataract prevention. Pyruvate also prevented the oxidative stress induced inhibition of retinal glycolysis. The primary aim of this study is hence to test further the effectiveness of pyruvate in preventing diabetes induced changes in lipid peroxidation, glutathione (GSH) oxidation and protein glycation in the mouse retina.
Diabetes was induced in C57Bl/6 mice by I.P. administration of streptozotocin. Diabetic animals were then divided into two groups. One group was treated with 3.5% ethyl pyruvate (EP) eye drops 6times/day and the other group served as untreated controls. Retinas were harvested after 8 weeks of diabetes and processed for measurements of GSH and malonaldehyde (MDA). Glycation was studied by determining incorporation of 5-3H glucose in the retinal proteins in the absence and presence of pyruvate.
GSH concentration in the retinas of diabetic mice decreased to ~70% of the normal. The level of MDA increased to 200% of the normal. The decrease in GSH and increase in MDA both were completely prevented by treatment with EP eye drops, their levels being close to the normal values in this group. Glycation was also inhibited substantially (by 70%) in the presence of pyruvate.
The results demonstrate for the first time that treatment with EP eye drops is significantly effective in preventing oxidative damage to the retina of diabetic mice. It is therefore hypothesized that use of pyruvate could be medically beneficial in ameliorating diabetic effects on the retina.
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