Effects of antioxidant gene therapy on the development of diabetic retinopathy and the metabolic memory phenomenon.

Abstract

PURPOSE:

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: Liwei Zhang, Huiming Xia, Qianqian Han, Baihua Chen
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 253 Issue 2 Pg. 249-59 (Feb 2015) ISSN: 1435-702X [Electronic] Germany
• PMID: 25301398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Catalase
• Superoxide Dismutase

Topics

• Animals
• Antioxidants
• Apoptosis
• Basement Membrane (ultrastructure)
• Capillaries (ultrastructure)
• Catalase (metabolism)
• Dependovirus (genetics)
• Diabetes Mellitus, Experimental (enzymology, pathology, therapy)
• Diabetic Retinopathy (enzymology, pathology, therapy)
• Enzyme-Linked Immunosorbent Assay
• Genetic Therapy
• Genetic Vectors
• Hyperglycemia (enzymology, therapy)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Intravitreal Injections
• Male
• Metabolism (physiology)
• Microscopy, Electron, Transmission
• Rats
• Rats, Sprague-Dawley
• Retinal Vessels (ultrastructure)
• Superoxide Dismutase (genetics, metabolism)