Suppression of complex I gene expression induces optic neuropathy

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Optic nerve degeneration is a feature common to diseases with mutations in genes that encode complex I of the respiratory chain. Vulnerability of this central nervous system tract is a mystery, because of the paucity of animal models used to investigate effects of the mutated DNA in tissues rather than isolated in cultured cells. Using a ribozyme designed to degrade the mRNA encoding a critical nuclear-encoded subunit gene of complex I (NDUFA1), we tested whether oxidative phosphorylation deficiency can recapitulate the optic neuropathy of mitochondrial disease. Injection of adeno-associated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
JournalAnnals of Neurology
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Mitochondrial Diseases
Optic Nerve Diseases
Catalytic RNA
Leber's Hereditary Optic Atrophy
Gene Expression
Nerve Degeneration
Dependovirus
Demyelinating Diseases
Optic Nerve
Electron Transport
Genes
Cultured Cells
Central Nervous System
Animal Models
Messenger RNA
Mutation
Injections
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Suppression of complex I gene expression induces optic neuropathy. / Qi, Xiaoping; Lewin, Alfred S.; Hauswirth, William W.; Guy, John.

In: Annals of Neurology, Vol. 53, No. 2, 01.02.2003, p. 198-205.

Research output: Contribution to journalArticle

Qi, Xiaoping ; Lewin, Alfred S. ; Hauswirth, William W. ; Guy, John. / Suppression of complex I gene expression induces optic neuropathy. In: Annals of Neurology. 2003 ; Vol. 53, No. 2. pp. 198-205.
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