Effect of Reinstitution of Good Glycemic Control on Retinal Oxidative Stress and Nitrative Stress in Diabetic Rats

Effect of Reinstitution of Good Glycemic Control on Retinal Oxidative Stress and Nitrative Stress in Diabetic Rats Renu A. Kowluru From the Kresge Eye Institute, Wayne State University, Detroit, Michigan Abstract Clinical and experimental studies have shown that reinstitution of good glycemic control (GC) after a period of poor glycemic control (PC) does not produce immediate benefits on the progression of retinopathy, and hyperglycemia is sufficient to initiate the development of diabetic retinopathy. In this study, the effect of reinstitution of GC on hyperglycemia-induced increased oxidative stress and nitrative stress was evaluated in the retina of rats maintained in PC before initiation of GC. In diabetic rats, 2 or 6 months of PC (GHb >11.0%) was followed by 7 months of GC (GHb 80% compared with normal rats or rats kept in GC for the duration. This suggests that oxidative and nitrative modifications in retina occur early in the course of development of retinopathy in diabetes. These abnormalities are not easily reversed by reinstitution of GC, and the duration of PC before initiation of GC influences the outcome of the reversal. Characterization of the abnormalities responsible for the resistance of retinopathy to arrest after reinstitution of GC will help identify potential future therapies to inhibit progression of diabetic retinopathy. Footnotes Address correspondence and reprint requests to Renu A. Kowluru, Kresge Eye Institute, Wayne State University, Detroit, MI 48201. E-mail: rkowluru{at}med.wayne.edu . Received for publication 20 August 2002 and accepted in revised form 2 December 2002. GC, good glycemic control; GSH, reduced glutathione; iNOS, inducible nitric oxide synthase; LPO, lipid peroxide; NO, nitric oxide; PC, poor glycemic control. DIABETES