Long–Term Administration of Lipoic Acid Inhibits Retinopathy in Diabetic Rats via Regulating Mitochondrial Superoxide Dismutase

Abstract

Abstract: : Purpose: Retinal mitochondria experience dysfunction in diabetes, and the therapies that inhibit superoxide production in the retina also inhibit the development of diabetic retinopathy. We have shown that long–term administration of lipoic acid has beneficial effects on the development of retinopathy in diabetic rats. The purpose of this study is to investigate the effect of administration of lipoic acid on the regulation of mitochondrial SOD (Mn–SOD) in the retina of diabetic rats. Methods: A group of streptozotocin diabetic rats received diet supplemented with or without α–lipoic acid (LA, 400mg/kg) for eleven months. The enzyme activity of SOD was measured using a kit from Cayman Chemical (Ann Arbor, MI) that utilizes tetrazolium salt to quantifying superoxide radicals. RNA was extracted by Trizol reagent, and reverse transcribed by the use of Sensiscript II Reverse transcriptase (Invitrogen, Carlsbad, CA). mRNA levels were quantified by real time RT–PCR using a Lightcycler from Roche Applied Science (Indianapolis, IN). Results: Mn–SOD activity was inhibited by over 30% in the retina of rats diabetic for eleven months, and its mRNA levels were reduced by 25% as compared with the values obtained from the age–matched normal rats. In the same diabetic animals, the number of apoptotic capillary cells and acellular capillaries was increased by 3–4 folds. LA administration for the entire duration of diabetes prevented diabetes–induced inhibition of retinal Mn–SOD activity and decrease in its mRNA levels. LA administration also inhibited increase in the number of apoptotic capillary cells and acellular capillaries in the retina of the same diabetic rats. Conclusions: Mitochondrial SOD is inhibited in the retina at duration of diabetes when retinopathy is developing; the therapy that inhibits retinal capillary cell apoptosis and histopathology in diabetic rats also prevents changes in retinal Mn–SOD. Thus, mitochondrial superoxides play an important role in the development of retinopathy in diabetes.

Keywords: diabetic retinopathy • antioxidants • mitochondria