The Protective Action Of MnSOD In The Metabolic Memory Phenomenon Of Diabetic Retinopathy

ObjectiveDiabetic retinopathy (DRP) is a leading cause of blindness in working age adults. Approximately95%of patients with Type1diabetes develop some degree of retinopathy within25years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify the retinal injuries of diabetic rats induced by STZ(streptozotocin) under chronic hyperglycemia and after reinstitution of euglycemia, and the protective effect of recombinant Adeno-associated virus on diabetic rats.MethodsExperimental diabetic model was induced by single intraperitoneal injection of STZ (streptozotocin) in rats. All rats were randomly assigned to four groups:normal control group:normal blood sugar group for12months (group A); hyperglycemia group:poor glycemic control for12months (group B); metabolic memory group:6months of poor glycemic control (glycated hemoglobin, GHb>11.0%) was followed by6additional months of good glycemic control (GHb<7.0%)(group C) Treatment group:intravitreal injection of rAAV-MnSOD at the fifth month in metabolic memory group.(group D). Basement membrane thickness and the ratio of pericyte area to total capillary cross-section area of retinal capillary in ganglion cells layer and visual cells layer were observed by transmission electron microscope. Apoptosis of retinal capillary was detected by TUNEL. The amount of acellular capillary was counted in PAS staining and the activity of MnSOD was measured by xanthine oxidase method.Results1. After the reinstitution of euglycemia, the basement membrane thickness of retinal capillary in ganglion cells layer and visual cells layer, apoptosis of retinal capillary and the amount of acellular capillary of metabolic memory group were keeping increased (compared with group A,P<0.01; compared with group B, P>0.05); the ratio of pericyte area to total capillary cross-section area of retinal capillary and the activity of MnSOD were keeping decreased (compared with group A,P<0.01; compared with group B, P>0.05).2. Pretreatment with intravitreal injection of rAAV-MnSOD can effectively increase the activities of MnSOD, prevent the thicken of the basement membrane thickness, apoptosis of retinal capillary and the amount of acellular capillary arised from metabolic memory (compared with group C, P<0.05), and also prevent the lessen of the ratio of pericyte area to total capillary cross-section area of retinal capillary (compared with group C, P<0.01).Conclusion 1. In diabetic rats which was induced by single injection of STZ(streptozotocin), the pathological changes of retinal capillary still persistently developed even after the reinstitution of euglycemia, reminding the existence of "metabolic memory" phenomenon.2. The activities of MnSOD were keeping decreased, which is one of the most important reasons that causes metabolic memory phenomenon.3. Over expression of MnSOD can effectively alleviate the pathological changes of retinal capillary.4. rAAV—MnSOD may be a potential therapy to prevent diabetic retinopathy and the metabolic memory phenomenon caused by hyperglycemia.