Peroxynitrite and oxidative damage in experimental autoimmune uveitis

Guey Shuang Wu, Jie Zhang, Narsing A. Rao

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Purpose. Results of previous study demonstrated the presence of superoxide and nitric oxide in experimental autoimmune uveitis (EAU). These two chemical entities have recently been shown to combine rapidly to form one of the most potent known biologic oxidants, peroxynitrite. As an extension of the previous study, the current study was proposed to determine whether peroxynitrite is generated in EAU and the site and extent of any oxidative damage thereby inflicted. Methods. Experimental uveitis was induced in Lewis rats with retinal S-antigen. The localization of peroxynitrite was carried out by immunohistochemical detection of its nitration product, nitrotyrosine, using polyclonal rabbit antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2-naphthoic acid hydrazide. This fluorescent product was also visualized by coupling with Fast Blue B. A confocal laser scanning microscope was used for detection. Results. In EAU, the peroxynitrite plaques were observed to concentrate in the photoreceptors but were also visible in some inner retinal areas, including ganglion cell layers, nerve fiber layers, and retinal blood vessels. The lipid peroxides were localized exclusively in the photoreceptors, concentrating in the vicinity of the infiltrating phagocytes but not localized on the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors were also generated by aerobically exposing the naive, open eyecups to a radical generator, 2,2'azobis(2-amidinopropane) hydrochloride. Conclusions. In EAU, there was a substantial concentration of peroxynitrite in the photoreceptors. The presence of this oxidant appears to correlate with the pathologic oxidation demonstrated in this area. The photoreceptors are especially prone to radical-induced lipid peroxidation caused by high concentration of docasahexaenoic acid that is contained in these structures.

Original languageEnglish (US)
Pages (from-to)1333-1339
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number7
StatePublished - 1997
Externally publishedYes

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Peroxynitrous Acid
Uveitis
Lipid Peroxides
Phagocytes
Oxidants
Arrestin
Retinal Vessels
Peroxides
Nerve Fibers
Superoxides
Ganglia
Lipid Peroxidation
Nitric Oxide
Lasers
Rabbits
Acids
Membranes
Antibodies

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Peroxynitrite and oxidative damage in experimental autoimmune uveitis. / Wu, Guey Shuang; Zhang, Jie; Rao, Narsing A.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 7, 1997, p. 1333-1339.

Research output: Contribution to journalArticle

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abstract = "Purpose. Results of previous study demonstrated the presence of superoxide and nitric oxide in experimental autoimmune uveitis (EAU). These two chemical entities have recently been shown to combine rapidly to form one of the most potent known biologic oxidants, peroxynitrite. As an extension of the previous study, the current study was proposed to determine whether peroxynitrite is generated in EAU and the site and extent of any oxidative damage thereby inflicted. Methods. Experimental uveitis was induced in Lewis rats with retinal S-antigen. The localization of peroxynitrite was carried out by immunohistochemical detection of its nitration product, nitrotyrosine, using polyclonal rabbit antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2-naphthoic acid hydrazide. This fluorescent product was also visualized by coupling with Fast Blue B. A confocal laser scanning microscope was used for detection. Results. In EAU, the peroxynitrite plaques were observed to concentrate in the photoreceptors but were also visible in some inner retinal areas, including ganglion cell layers, nerve fiber layers, and retinal blood vessels. The lipid peroxides were localized exclusively in the photoreceptors, concentrating in the vicinity of the infiltrating phagocytes but not localized on the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors were also generated by aerobically exposing the naive, open eyecups to a radical generator, 2,2'azobis(2-amidinopropane) hydrochloride. Conclusions. In EAU, there was a substantial concentration of peroxynitrite in the photoreceptors. The presence of this oxidant appears to correlate with the pathologic oxidation demonstrated in this area. The photoreceptors are especially prone to radical-induced lipid peroxidation caused by high concentration of docasahexaenoic acid that is contained in these structures.",
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N2 - Purpose. Results of previous study demonstrated the presence of superoxide and nitric oxide in experimental autoimmune uveitis (EAU). These two chemical entities have recently been shown to combine rapidly to form one of the most potent known biologic oxidants, peroxynitrite. As an extension of the previous study, the current study was proposed to determine whether peroxynitrite is generated in EAU and the site and extent of any oxidative damage thereby inflicted. Methods. Experimental uveitis was induced in Lewis rats with retinal S-antigen. The localization of peroxynitrite was carried out by immunohistochemical detection of its nitration product, nitrotyrosine, using polyclonal rabbit antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2-naphthoic acid hydrazide. This fluorescent product was also visualized by coupling with Fast Blue B. A confocal laser scanning microscope was used for detection. Results. In EAU, the peroxynitrite plaques were observed to concentrate in the photoreceptors but were also visible in some inner retinal areas, including ganglion cell layers, nerve fiber layers, and retinal blood vessels. The lipid peroxides were localized exclusively in the photoreceptors, concentrating in the vicinity of the infiltrating phagocytes but not localized on the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors were also generated by aerobically exposing the naive, open eyecups to a radical generator, 2,2'azobis(2-amidinopropane) hydrochloride. Conclusions. In EAU, there was a substantial concentration of peroxynitrite in the photoreceptors. The presence of this oxidant appears to correlate with the pathologic oxidation demonstrated in this area. The photoreceptors are especially prone to radical-induced lipid peroxidation caused by high concentration of docasahexaenoic acid that is contained in these structures.

AB - Purpose. Results of previous study demonstrated the presence of superoxide and nitric oxide in experimental autoimmune uveitis (EAU). These two chemical entities have recently been shown to combine rapidly to form one of the most potent known biologic oxidants, peroxynitrite. As an extension of the previous study, the current study was proposed to determine whether peroxynitrite is generated in EAU and the site and extent of any oxidative damage thereby inflicted. Methods. Experimental uveitis was induced in Lewis rats with retinal S-antigen. The localization of peroxynitrite was carried out by immunohistochemical detection of its nitration product, nitrotyrosine, using polyclonal rabbit antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2-naphthoic acid hydrazide. This fluorescent product was also visualized by coupling with Fast Blue B. A confocal laser scanning microscope was used for detection. Results. In EAU, the peroxynitrite plaques were observed to concentrate in the photoreceptors but were also visible in some inner retinal areas, including ganglion cell layers, nerve fiber layers, and retinal blood vessels. The lipid peroxides were localized exclusively in the photoreceptors, concentrating in the vicinity of the infiltrating phagocytes but not localized on the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors were also generated by aerobically exposing the naive, open eyecups to a radical generator, 2,2'azobis(2-amidinopropane) hydrochloride. Conclusions. In EAU, there was a substantial concentration of peroxynitrite in the photoreceptors. The presence of this oxidant appears to correlate with the pathologic oxidation demonstrated in this area. The photoreceptors are especially prone to radical-induced lipid peroxidation caused by high concentration of docasahexaenoic acid that is contained in these structures.

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