HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Qi, X. Articles by Guy, J. Search for Related Content PubMed PubMed Citation Articles by Qi, X. Articles by Guy, J.

Suppression of Mitochondrial Oxidative Stress Provides Long-term Neuroprotection in Experimental Optic Neuritis

¹From the Departments of Ophthalmology, ²Molecular Genetics and Microbiology, and ³Neurology, University of Florida, College of Medicine, Gainesville, Florida.

PURPOSE. Axonal loss is thought to contribute to the persistence of visual loss in optic neuritis and multiple sclerosis (MS). The mechanisms of injury are poorly understood. The authors investigated the contribution of mitochondrial oxidative stress and the effects of modulating mitochondrial antioxidant gene expression in the optic nerves of mice induced with experimental allergic encephalomyelitis (EAE), with a focus on long-term neuroprotection.

METHODS. Optic nerves from mice with EAE were probed for reactive oxygen species (ROS) with the use of dichlorofluorescein diacetate (DCFDA), dihydroethidium, and cerium chloride. To modulate mitochondrial oxidative stress, recombinant AAV containing the human SOD2 gene or a ribozyme targeting murine SOD2 was injected into the vitreous. Control eyes received the recombinant virus without a therapeutic gene. Mice were sensitized for EAE and were monitored by serial contrast-enhanced MRI. The effects of SOD2 modulation on the EAE optic nerve were gauged by computerized analysis of optic nerve volume, myelin fiber area, and retinal ganglion cell loss at 1, 3, and 12 months after sensitization for EAE.

RESULTS. ROS were detected in the EAE optic nerve as early as 3 days after antigenic sensitization. Colocalization suggested mitochondria as the source of ROS activity in the absence of inflammation. The ribozyme suppressing SOD2 gene expression increased myelin fiber injury by 27%. Increasing SOD2 levels twofold in the optic nerve by virally mediated gene transfer ameliorated myelin fiber injury by 51% and RGC loss fourfold, limiting it to 7% in EAE at 1 year.

CONCLUSIONS. Amelioration of mitochondrial oxidative stress by SOD2 gene delivery may be a therapeutic strategy for suppressing neurodegeneration in optic neuritis.

This article has been cited by other articles:

				K. S. Shindler, L. C. Kenyon, M. Dutt, S. T. Hingley, and J. D. Sarma Experimental Optic Neuritis Induced by a Demyelinating Strain of Mouse Hepatitis Virus J. Virol., September 1, 2008; 82(17): 8882 - 8886. [Abstract] [Full Text] [PDF]

				X. Qi, L. Sun, A. S. Lewin, W. W. Hauswirth, and J. Guy Long-term Suppression of Neurodegeneration in Chronic Experimental Optic Neuritis: Antioxidant Gene Therapy Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5360 - 5370. [Abstract] [Full Text] [PDF]

				K. S. Shindler, E. Ventura, T. S. Rex, P. Elliott, and A. Rostami SIRT1 Activation Confers Neuroprotection in Experimental Optic Neuritis Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3602 - 3609. [Abstract] [Full Text] [PDF]