Peroxynitrite and oxidative damage in experimental autoimmune uveitis

Area of Science:

• Ophthalmology
• Immunology
• Biochemistry

Background:

• Previous studies identified superoxide and nitric oxide in experimental autoimmune uveitis (EAU).
• Superoxide and nitric oxide combine to form peroxynitrite, a potent biologic oxidant.
• The role and location of peroxynitrite generation in EAU were previously unknown.

Purpose of the Study:

• To determine if peroxynitrite is generated in EAU.
• To identify the location and extent of oxidative damage caused by peroxynitrite in EAU.
• To investigate the correlation between peroxynitrite and photoreceptor damage in EAU.

Main Methods:

• Experimental autoimmune uveitis (EAU) was induced in Lewis rats using retinal S-antigen.
• Immunohistochemistry detected peroxynitrite by identifying its nitration product, nitrotyrosine.
• Lipid peroxides were detected using fluorescent labeling, and visualization was performed with confocal laser scanning microscopy.

Main Results:

• Peroxynitrite plaques were concentrated in photoreceptors and also found in inner retinal areas and blood vessels.
• Lipid peroxides were exclusively localized in photoreceptors, near infiltrating phagocytes.
• Photoreceptor peroxide lesions were replicated by exposing naive eyecups to a radical generator.

Conclusions:

• Substantial peroxynitrite concentration was observed in the photoreceptors during EAU.
• Peroxynitrite presence correlates with pathological oxidation in the photoreceptor layer.
• Photoreceptors are susceptible to radical-induced lipid peroxidation due to high docasahexaenoic acid content.