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SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I
Author(s) -
Qi Xiaoping,
Lewin Alfred S.,
Sun Liang,
Hauswirth William W.,
Guy John
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20175
Subject(s) - optic neuropathy , sod2 , optic nerve , mitochondrial disease , lactic acidosis , leber's hereditary optic neuropathy , respiratory chain , mitochondrial encephalomyopathy , mitochondrial respiratory chain , medicine , mitochondrion , sod1 , biology , mitochondrial dna , pathology , disease , neuroscience , genetics , gene , oxidative stress , amyotrophic lateral sclerosis , superoxide dismutase
Mutations in genes encoding the NADH ubiquinone oxidoreductase, complex I of the respiratory chain, cause a diverse group of diseases. They include Leber hereditary optic neuropathy, Leigh syndrome, and mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes. There is no effective treatment for these or any other mitochondrial disorder. Using a unique animal model of severe complex I deficiency induced by ribozymes targeted against a critical complex I subunit gene (NDUFA1), we attempted rescue of the optic nerve degeneration associated with Leber hereditary optic neuropathy. We used adenoassociated virus to deliver the human gene for SOD2 to the visual system of disease‐induced mice. Relative to mock infection, SOD2 reduced apoptosis of retinal ganglion cells and degeneration of optic nerve fibers, the hallmarks of this disease. Rescue of this animal model supports a critical role for oxidative injury in disorders with complex I deficiency and shows that a respiratory deficit may be effectively treated in mammals, thus offering hope to patients. Ann Neurol 2004;56:182–191