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• W2069376449 abstract "<h3>Objective</h3> To explore a treatment paradigm for Leber hereditary optic neuropathy (LHON), we augmented mitochondrial antioxidant defenses to rescue cells with the G11778A mutation in mitochondrial DNA. <h3>Methods</h3> Cells homoplasmic for the G11778A mutation in mitochondrial DNA were infected with an adeno-associated viral vector containing the human mitochondrial superoxide dismutase (<i>SOD2</i>) gene. Control cells were infected with an adeno-associated viral (AAV) vector expressing the green fluorescent protein (GFP). Two days later, the high-glucose culture medium was exchanged for a glucose-free medium containing galactose. After 1 or 2days, cellular production of superoxide was assessed using the fluorescent probe dihydroethidium, and we used TUNEL (terminal deoxynucleotidyl transferase–mediated biotin–deoxyuridine triphosphate nick-end labeling) staining to detect apoptotic nuclei. The effect of<i>SOD2</i>on LHON cell survival was quantitated after 2 or 3 days. <h3>Results</h3> Comparisons of AAV-<i>SOD2</i>–infected LHON cells relative to control cells infected with AAV–green fluorescent protein showed increased expression of mitochondrial SOD that attenuated superoxide-induced fluorescence by 26% (<i>P</i> = .003) and suppressed TUNEL-induced fluorescence by 21% (<i>P</i> = .048)after 2 days of growth in galactose medium, when cell survival increased by 25% (<i>P</i>=.05). After 3 days in galactose medium,<i>SOD2</i>increased LHON survival by 89% (<i>P</i> = .006) relative to controls. <h3>Conclusion</h3> Protection against mitochondrial oxidative stress may be useful for treatment of LHON. <h3>Clinical Relevance</h3> Gene therapy with antioxidant genes may protect patients with LHON against visual loss." @default.
• W2069376449 created "2016-06-24" @default.
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• W2069376449 date "2007-02-01" @default.
• W2069376449 modified "2023-09-25" @default.
• W2069376449 title "Use of Mitochondrial Antioxidant Defenses for Rescue of Cells With a Leber Hereditary Optic Neuropathy–Causing Mutation" @default.
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• W2069376449 doi "https://doi.org/10.1001/archopht.125.2.268" @default.
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