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T.S. Rex, J. Bennett, A.M. Maguire, J.L. Dunaief; Adeno-Catalase Protects the Balb/c Mouse Retina from Light-Damage . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1082.
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Purpose: To protect the retina from light induced oxidative stress by over-expressing the antioxidant enzyme, catalase, by gene therapy. Methods: Adeno-CMV-catalase or adeno-lacZ were injected into the subretinal space of Balb/c mice 1 day prior to light-damage. Mice were submitted to 7 hours of 8,000lux white fluorescent light then dark-adapted for 24 hours. Mice were euthanized and enucleated and the eyes were fixed for 2 hrs in 4% paraformaldehyde. TUNEL, and immunohistochemistry were performed on 10µm thick frozen sections. Sections were labeled with anti-catalase, anti-Cu,Zn-SOD, anti-Mn-SOD or anti-HNE. Results: Many TUNEL-positive nuclei were found in the light-damaged retinas injected with adeno-lacZ, but very few were found in light-damaged retinas injected with adeno-catalase. Immunolabeling of adeno-catalase treated, light-damaged retinas with the various antibodies was similar to the normal, uninjected retinas. In contrast, immunolabeling of adeno-lacZ injected, light-damaged retinas with anti-HNE, anti-Mn-SOD, and anti-Cu,Zn-SOD was increased over controls. Conclusions: As reported previously, the increases in Mn-SOD, Cu,Zn-SOD, and HNE immunolabeling are indicative of oxidative stress. Catalase over-expression in the RPE by gene transfer with adeno-catalase is able to prevent lipid peroxidation and apoptosis due to light-damage. These results implicate hydrogen peroxide, the catalase substrate, in the pathogenesis of photic injury and provide a paradigm for antioxidant gene therapy in retinal degenerations involving photo-oxidative stress.
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