Influence of antioxidant enzymes in reduction of optic disc edema in experimental optic neuritis

Guy, John; Ellis, E. Ann; Hope, G. M.; Rao, Narsing A.

doi:10.1016/s0748-5514(86)80035-6

Cited by 22 publications

(9 citation statements)

References 23 publications

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“…Accumulation of H 2 O 2 is suppressed by antioxidant enzymes such as catalase. Although the role of catalase in suppressing demyelination had previously implicated H 2 O 2 in the pathogenesis of CNS demyelination (12,13,15,19), genetically increasing catalase levels in oligodendroglia with a single inoculation reduced demyelination as much as 38%, thus partially protecting these important cells from the adverse effects of H 2 O 2 released into the microenvironment by the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

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Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis

Guy

Hauswirth

1998

Proc. Natl. Acad. Sci. U.S.A.

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Suppression of oxidative injury by viralmediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inf lammatory autoimmune 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 common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL͞J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H 2 O 2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H 2 O 2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.

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Section: Discussionmentioning

confidence: 99%

“…The role of ROS in altering BBB permeability and demyelination has been inferred from the beneficial effect of free radical scavengers and antioxidants on the neurologic deficits and histopathologic lesions associated with EAE (11)(12)(13)(14)(15)(16)(17). ROS scavengers include catalase and superoxide dismutase.…”

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confidence: 99%

Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis

Guy

Hauswirth

1998

Proc. Natl. Acad. Sci. U.S.A.

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“…Reactive oxygen species such as H2O2 play a role in the pathogenesis of demyelination in EAE [3, [18][19][20]. In this study, we have direct ly demonstrated significant amounts of H2O2-derived cerium perhydroxide reaction prod uct in the myelinated retrobulbar optic nerve during the early preclinical phase of EAE, 3 days after antigenic sensitization, a time peri od when disruption of the blood-brain barrier first occurs [16,[21][22][23].…”

Section: Discussionmentioning

confidence: 89%

“…In this study, we have direct ly demonstrated significant amounts of H2O2-derived cerium perhydroxide reaction prod uct in the myelinated retrobulbar optic nerve during the early preclinical phase of EAE, 3 days after antigenic sensitization, a time peri od when disruption of the blood-brain barrier first occurs [16,[21][22][23]. Since most reactive oxygen species are extremely reactive and are difficult to demonstrate directly [1, 2], the role of reactive oxygen species had been im plicated indirectly by reductions in edema and demyelination of the optic nerve with administration of antioxidant enzymes that detoxify H2O2 [3,19,20], Consumption of H2O2 as demyelination advances in the retrobulbar optic nerve 7-14 days after sensitization, may be due to conver sion of H2O2 to other reactive oxygen species [1,2,8,9] contributing to the reductions of H20 2-derived cerium perhydroxide reaction product we observed 7-14 days after antigen ic sensitization. Hydrogen peroxide may re sult in peroxidation of myelin lipid directly or by conversion to hydroxyl radicals or lipid free radicals [5,17,18], These free radicals may in turn generate additional free radicals resulting in further peroxidation of myelin lipid and amplification of demyelination [6].…”

Section: Discussionmentioning

confidence: 99%

Role of Hydrogen Peroxide in Experimental Optic Neuritis

Guy

Ellis²,

Mames³

et al. 1993

Ophthalmic Res

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In order to determine the role of H₂O₂in demyelination of the optic nerve, serial quantitative analysis of H₂O₂-derived cerium perhydroxide reaction product particles was obtained by computerized digitization of electron micrographs of the myelinated retrobulbar optic nerve, unmyelinated optic nerve head, and the optic nerve sheath of guinea pigs sensitized for experimental allergic encephalomyelitis (EAE) and euthanized 3-14 days later. We found that cerium perhydroxide reaction product particles were greatest in the myelinated optic nerve 3 days after antigenic sensitization, but at this focus decreased 7–14 days after antigenic sensitization. Reaction product accumulated in the unmyelinated optic nerve head and optic nerve sheath 3–14 days after sensitization. These results in the myelinated optic nerve suggest H₂O₂ consumption results in peroxidation of myelin lipid as demyelination proceeds 7–14 days after antigenic sensitization. Hydrogen peroxide accumulation in the optic nerve head and the optic nerve sheath appears to provide a reservoir for diffusion of H₂O₂ into the retrobulbar optic nerve and adjacent perineural nerve, contributing to the frequent predilection for optic nerve involvement in EAE and perhaps in multiple sclerosis.

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“…Although a variety of antioxidants have been shown to prevent and/or suppress severity of EAE, the use of dietary antioxidants such as vitamins C and E, and lipoic acid evinced mixed results in MS patients (Gilgun-Sherki et al, 2004; van Meeteren et al, 2004; Schreibelt et al, 2007). Furthermore, in EAE models, therapeutic administration of SOD yielded little or no effects, but was found to be beneficial in disease models for experimental optic neuritis and uveoretinitis including neuronal injuries (Guy et al, 1986; Yamada et al, 1986; Guy et al, 1989; Barkats et al, 1996; Chan et al, 1998; Qi et al, 2007). These observations raise a question as to the functional role of SODs in various organ-specific autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Copper–zinc superoxide dismutase-deficient mice show increased susceptibility to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein 35–55

Massilamany

Gangaplara

Kim

et al. 2013

Journal of Neuroimmunology

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In this report, we have addressed the role of copper–zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35–55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance of self-tolerance leading to the suppression of autoimmune responses.

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Influence of antioxidant enzymes in reduction of optic disc edema in experimental optic neuritis

Cited by 22 publications

References 23 publications

Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis

Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis

Role of Hydrogen Peroxide in Experimental Optic Neuritis

Copper–zinc superoxide dismutase-deficient mice show increased susceptibility to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein 35–55

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