Dual gene therapy with extracellular superoxide dismutase and catalase attenuates experimental optic neuritis

Xiaoping Qi, William W. Hauswirth, John Guy

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose: To ameliorate experimental optic neuritis by combining scavenging of superoxide by germ line increases in the extracellular superoxide dismutase (ECSOD) and hydrogen peroxide by viral-mediated gene transfer of the human catalase gene. Methods: The human catalase gene inserted into recombinant adeno-associated virus (rAAV) was injected into the right eyes of transgenic mice overexpressing human ECSOD and wild-type littermates. Animals were simultaneously sensitized for experimental autoimmune encephalomyelitis (EAE) and then sacrificed one month later. The effects of antioxidant genes (ECSOD and catalase) on the histologic lesions of EAE were measured by computerized analysis of myelin area, optic disc area, extent of the cellular infiltrate, cerium derived H2O2 reaction product and extravasation of serum albumin detected by immunogold. Results: Combined scavenging of H2O2 and superoxide with ECSOD and catalase suppressed demyelination by 72%, 54% due to catalase, and 19% due to ECSOD. Disruption of the blood-brain barrier was reduced 63% by the combined effects of catalase and ECSOD, 35% due to catalase and 29% due to ECSOD. Conclusions: Transgene modulation of antioxidant enzyme defenses against both superoxide and its metabolite H2O2 provide a substantial suppressive effect against EAE in the optic nerve that may be a new therapeutic strategy for suppression of optic neuritis and multiple sclerosis.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalMolecular Vision
Volume13
StatePublished - Jan 5 2007
Externally publishedYes

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Optic Neuritis
Genetic Therapy
Catalase
Superoxide Dismutase
Autoimmune Experimental Encephalomyelitis
Superoxides
Antioxidants
Genes
Cerium
Dependovirus
Viral Genes
Optic Disk
Demyelinating Diseases
Optic Nerve
Myelin Sheath
Blood-Brain Barrier
Transgenes
Germ Cells
Serum Albumin
Hydrogen Peroxide

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Dual gene therapy with extracellular superoxide dismutase and catalase attenuates experimental optic neuritis. / Qi, Xiaoping; Hauswirth, William W.; Guy, John.

In: Molecular Vision, Vol. 13, 05.01.2007, p. 1-11.

Research output: Contribution to journalArticle

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N2 - Purpose: To ameliorate experimental optic neuritis by combining scavenging of superoxide by germ line increases in the extracellular superoxide dismutase (ECSOD) and hydrogen peroxide by viral-mediated gene transfer of the human catalase gene. Methods: The human catalase gene inserted into recombinant adeno-associated virus (rAAV) was injected into the right eyes of transgenic mice overexpressing human ECSOD and wild-type littermates. Animals were simultaneously sensitized for experimental autoimmune encephalomyelitis (EAE) and then sacrificed one month later. The effects of antioxidant genes (ECSOD and catalase) on the histologic lesions of EAE were measured by computerized analysis of myelin area, optic disc area, extent of the cellular infiltrate, cerium derived H2O2 reaction product and extravasation of serum albumin detected by immunogold. Results: Combined scavenging of H2O2 and superoxide with ECSOD and catalase suppressed demyelination by 72%, 54% due to catalase, and 19% due to ECSOD. Disruption of the blood-brain barrier was reduced 63% by the combined effects of catalase and ECSOD, 35% due to catalase and 29% due to ECSOD. Conclusions: Transgene modulation of antioxidant enzyme defenses against both superoxide and its metabolite H2O2 provide a substantial suppressive effect against EAE in the optic nerve that may be a new therapeutic strategy for suppression of optic neuritis and multiple sclerosis.

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