Use of mitochondrial antioxidant defenses for rescue of cells with a leber hereditary optic neuropathy-causing mutation

Xiaoping Qi, Liang Sun, William W. Hauswirth, Alfred S. Lewin, John Guy

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Objective: 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. Methods: Cells homoplasmic for the G11778A mutation in mitochondrial DNA were infected wit h an adeno-associated viral vector containing the human mitochondrial superoxide dismutase (SOD2) 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 2 days, 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 SOD2 on LHON cell survival was quantitated after 2 or 3 days. Results: Comparisons of AAV-SOD2-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% (P=.003) and suppressed TUNEL-induced fluorescence by 21% (P=.048) after 2 days of growth in galactose medium, when cell survival increased by 25% (P=.05). After 3 days in galactose medium, SOD2 increased LHON survival by 89% (P=.006) relative to controls. Conclusion: Protection against mitochondrial oxidative stress may be useful for treatment of LHON. Clinical Relevance: Gene therapy with antioxidant genes may protect patients with LHON against visual loss.

Original languageEnglish (US)
Pages (from-to)268-272
Number of pages5
JournalArchives of ophthalmology
Issue number2
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology


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