Suppression of complex I gene expression induces optic neuropathy

Ann Neurol. 2003 Feb;53(2):198-205. doi: 10.1002/ana.10426.


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 adenoassociated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adenoviridae / genetics
  • Animals
  • Electron Transport Complex I
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Kidney / cytology
  • Mice
  • Mitochondria / enzymology
  • NADH, NADPH Oxidoreductases / genetics*
  • Optic Nerve / enzymology
  • Optic Nerve / pathology
  • Optic Nerve / physiopathology
  • Optic Nerve Diseases / enzymology
  • Optic Nerve Diseases / pathology
  • Optic Nerve Diseases / physiopathology*
  • RNA, Catalytic / metabolism
  • RNA, Catalytic / pharmacology
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics


  • RNA, Catalytic
  • RNA, Messenger
  • Recombinant Proteins
  • hammerhead ribozyme
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I