SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalAnnals of Neurology
Volume56
Issue number2
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Fingerprint

Optic Nerve Diseases
Leber's Hereditary Optic Atrophy
Optic Nerve
Animal Models
MELAS Syndrome
Leigh Disease
Genes
Electron Transport Complex I
Mitochondrial Diseases
Nerve Degeneration
Catalytic RNA
Retinal Ganglion Cells
Electron Transport
Nerve Fibers
Mammals
Apoptosis
Viruses
Mutation
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. / Qi, Xiaoping; Lewin, Alfred S.; Sun, Liang; Hauswirth, William W.; Guy, John.

In: Annals of Neurology, Vol. 56, No. 2, 01.08.2004, p. 182-191.

Research output: Contribution to journalArticle

Qi, Xiaoping ; Lewin, Alfred S. ; Sun, Liang ; Hauswirth, William W. ; Guy, John. / SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. In: Annals of Neurology. 2004 ; Vol. 56, No. 2. pp. 182-191.
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