Dual gene therapy with extracellular superoxide dismutase andcatalase attenuates experimental optic neuritis

[摘要] Purpose: To ameliorate experimental optic neuritis by combiningscavenging of superoxide by germ line increases in the extracellularsuperoxide dismutase (ECSOD) and hydrogen peroxide by viral-mediatedgene transfer of the human catalase gene.Methods: The human catalase gene inserted into recombinantadeno-associated virus (rAAV) was injected into the right eyes oftransgenic mice overexpressing human ECSOD and wild-type littermates.Animals were simultaneously sensitized for experimental autoimmuneencephalomyelitis (EAE) and then sacrificed one month later. The effectsof antioxidant genes (ECSOD and catalase) on the histologic lesions ofEAE were measured by computerized analysis of myelin area, optic discarea, extent of the cellular infiltrate, cerium derived H2O2reaction product and extravasation of serum albumin detected byimmunogold.Results: Combined scavenging of H2O2 and superoxide withECSOD and catalase suppressed demyelination by 72%, 54% due to catalase,and 19% due to ECSOD. Disruption of the blood-brain barrier was reduced63% by the combined effects of catalase and ECSOD, 35% due to catalaseand 29% due to ECSOD.Conclusions: Transgene modulation of antioxidant enzyme defensesagainst both superoxide and its metabolite H2O2 provide asubstantial suppressive effect against EAE in the optic nerve that maybe a new therapeutic strategy for suppression of optic neuritis andmultiple sclerosis.

[学科分类] 生物化学/生物物理