Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis.

Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Research Abstract Details 

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Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Abstract Text:

Xiaoping Qi,Alfred S Lewin,Liang Sun,William W Hauswirth,John Guy,

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.

Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Publishing Authors By Initials

X Qi,AS Lewin,L Sun,WW Hauswirth,J Guy,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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MEDLINE DATE:

Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Investigative ophthalmology & visual science

VOLUME: 48

Page Numbers: 681-91

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 3

MONTH: Feb

YEAR: 2007

Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7703701

Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Information

Substance Name: superoxide dismutase 2

Registry Number: EC 1.15.1.1

Grant and Affiliation Information for Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis.

AFFILIATION: Department of Ophthalmology, University of Florida, College of Medicine, Gainesville, FL 32610-0284, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY12355

ACRONYM: EY

MEDLINETA: Invest Ophthalmol Vis Sci

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