Retinal mitochondria experience increased oxidative damage in diabetes, and complex III is one of the sources of increased superoxide. MnSOD protects the retina from diabetes-induced abnormalities in the mitochondria and prevents vascular histopathology, strongly implicating the role for MnSOD in the pathogenesis of retinopathy in diabetes.

Background: Oxidative stress and inflammation are implicated in the pathogenesis of retinopathy in diabetes. The aim of this study is to examine the effect of curcumin, a polyphenol with antioxidant and anti-inflammatory properties, on diabetes-induced oxidative stress and inflammation in the retina of rats.

Diabetic retinopathy does not halt after hyperglycemia is terminated; the retina continues to experience increased oxidative stress, suggesting a memory phenomenon. Mitochondrial DNA (mtDNA) is highly sensitive to oxidative damage. The goal is to investigate the role of mtDNA damage in the development of diabetic retinopathy, and in the metabolic memory. mtDNA damage and its functional consequences on electron transport chain (ETC) were analyzed in the retina from streptozotocin-diabetic rats maintained in poor control (PC, glycated hemoglobin >11%) for 12 months or PC for 6 months followed by good control (GC, GHb < 6.5%) for 6 months. Diabetes damaged retinal mtDNA and elevated DNA repair enzymes (glycosylase). ETC proteins that were encoded by the mitochondrial genome and the glycosylases were compromised in the mitochondria. Re-institution of GC after 6 months of PC failed to protect mtDNA damage, and ETC proteins remained subnormal. Thus, mtDNA continues to be damaged even after PC is terminated. Although the retina tries to overcome mtDNA damage by inducing glycosylase, they remain deficient in the mitochondria with a compromised ETC system. The process is further exacerbated by subsequent increased mtDNA damage providing no relief to the retina from a continuous cycle of damage, and termination of hyperglycemia fails to arrest the progression of retinopathy.