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M.S. Ola, Y. Xu, D. Berkich, K. LaNoue, I. Simpson; Effect of Diabetes and Hyperglycemia on Retinal Metabolism and Redox State. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3226.
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Purpose: Growing evidence suggests that excessive reactive oxygen species may be an underlying cause of diabetic retinopathy. It has been reported that hyperglycemia and/or diabetes exert increased reductive stress (NADH/NAD+ ratio) on the mitochondria, accelerating electron flow to O2 and thereby producing oxygen free radicals. The purpose of this study was to test the hypothesis that elevated glucose increases mitochondrial metabolism leading to generation of reactive oxygen species. Methods: Rat retinas were excised from control and from 3–4 weeks streptozotocin–diabetic rats (65 mg/kg), incubated in physiological media with either 5 or 20 mM glucose. We measured the rate of glycolysis, lactic acid production, the rate of CO2 formation and glutamate synthesis. Glycolytic flux was measured by 3H2O release from 5–3H–glucose. U–14C–glucose was used to measure 14C–glutamate, 14C–lactate and 14CO2 production. Total glutamate and lactate were determined enzymatically. Results:The rate of glycolysis was only slightly higher under hyperglycemic compared to euglycemic conditions and did not differ between control and diabetic retinas. There was no significant difference in lactate/pyruvate ratio in control versus diabetic retina under normal and hyperglycemic conditions. Citric acid cycle was unaffected by 5 or 20 mM glucose in normal retina. However, diabetes downregulated the citric acid cycle flux in excised retina. Elevated glucose (20 mM) normalized the citric acid cycle rate of diabetic retina with respect to those of control retina. 14C–glutamate production mirrored the 14CO2 data but glutamate mass tended to decline faster in control than diabetic retinas. Conclusions:Our data do not support the role of hyperglycemia in superoxide production but do not rule out a role for superoxide production in the etiology of diabetic retinopathy.
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