ADENOASSOCIATED VIRAL-MEDIATED CATALASE EXPRESSION SUPPRESSES OPTIC NEURITIS IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Suppression of oxidative injury by viral-mediated transfer of the huma n catalase gene was tested in the optic nerves of animals with experim ental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimm une disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement com mon to both EAE and MS. Recombinant adeno-associated virus containing the human gene far catalase was injected over the right optic nerve he ads of SJL/J mice that mere simultaneously sensitized for EAE, After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endoth elia, oligodendroglia, astrocytes, and axons of the optic nerve, Effec ts of catalase on the histologic lesions of EAE were measured by compu terized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infi ltrate, extravasated serum albumin labeled by immunogold (for blood-br ain barrier disruption), and in vivo H2O2 reaction product. Relative t o control, contralateral optic nerves injected with the recombinant vi rus without a therapeutic gene, catalase gene inoculation reduced demy elination by 38%, optic nerve head swelling by 29%, cellular infiltrat ion by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments fo r MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a t herapeutic strategy for suppression of MS.