title: Effects of antioxidant gene therapy on the development of diabetic retinopathy and the metabolic memory phenomenon.
abstract: OBJECTIVE
  The purpose of this study was to determine the therapeutic effect and mechanism of AAV-MnSOD by intravitreal injection on diabetic retinopathy (DRP) and the metabolic memory phenomenon.
  
  
  METHODS
  The effect of hyperglycemia and metabolic memory on the thickness of basement membrane, ratio of pericyte area and cross-sectional area of capillary vessels in the nerve fiber layer and outer plexiform layer; retinal capillary cell apoptosis; number of acellular capillaries and activities of retinal MnSOD and catalase were examined and compared with intravitreal injection of AAV-MnSOD by transmission electron microscopy, TUNEL assay, ELISA, and immunohistochemistry.
  
  
  RESULTS
  Hyperglycemia increased the thickness of capillary basement membranes in the nerve fiber layer and outer plexiform layer, decreased the ratio of pericyte area and cross-sectional area of capillary vessels, increased numbers of acellular capillaries and apoptosis of retinal capillary cells, and decreased activities of retinal MnSOD and catalase. Termination of hyperglycemia cannot reverse pathological changes listed above. Intra-vitreal injection of AAV-MnSOD dramatically elevated the level and activities of retinal MnSOD and catalase, and effectively prevented the progression of DRP and the metabolic memory phenomenon.
  
  
  CONCLUSIONS
  Increasing reactive oxygen species concentration and continuous decreasing of antioxidant enzyme activity play important roles in DRP and the metabolic memory phenomenon. AAV-MnSOD gene therapy provides a promising strategy to inhibit this blinding disease.
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha Hunan Province, People's Republic of China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.forename: Huiming
authors.initials: H
authors.lastname: Xia
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.forename: Baihua
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants; D017209:Apoptosis; D001485:Basement Membrane / Q000648:ultrastructure; D002196:Capillaries / Q000648:ultrastructure; D002374:Catalase / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005822:Genetic Vectors; D006943:Hyperglycemia / Q000201:enzymology / Q000628:therapy; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D058449:Intravitreal Injections; D008297:Male; D008660:Metabolism / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002374:Catalase; D013482:Superoxide Dismutase