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M Schwartz, T Mizrahi; Pathogenic Self-antigens In Autoimmune Disease Are Potentially Protective: A Lesson From The Visual System . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1538.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the effect of a T cell-mediated autoimmune response induced by immunization with uveitogenic retinal antigens on the survival of retinal ganglion cells (RGCs), in a rat model of optic nerve crush or glutamate toxicity. Methods: Adult Lewis, SPD and Fisher rats were subjected to either partial optic nerve crush injury or intravitreous injection of toxic concentrations of glutamate. Rats were immediately immunized with 30 µg of R16 (ADGSSWEGVGVVPDV), a peptide derived from IRBP, emulsified in CFA. Control rats were injected with PBS in CFA. Two weeks later, the fluorescent dye 4-Di-10-Asp was applied to the nerve distally to the site of injury. After 5 days retinas were detached from the eyes, prepared as flattened whole mounts, and examined for labeled RGCs by fluorescence microscopy. Results: Significantly more RGCs (mean SEM per mm2) survived in the immunized injured rats than in their matched PBS-injected controls (150 13 and 6014 respectively, P<0.01 for SPD rats; 1928 and 7310 respectively, P<0.0001 for Lewis rats; 183 16 and 1149 respectively, P<0.01 for Fisher rats). The number of surviving RGCs in Fisher rats that were immunized with R16 after exposure to glutamate toxicity was significantly higher than in the matched PBS-injected controls (192847 and 161787 respectively, P < 0.05). Conclusion: We show that a self-antigen associated with uveitis reduces RGCs loss resulting from either glutamate toxicity or axonal injury. These results suggest that as in the case of myelin-associated antigens, the protective antigen for RGCs is identical to the self-pathogen associated with the common autoimmune disease in this tissue (i.e. uveitis). Based on our results we propose a more general phenomenon: pathogenic-self antigens in autoimmune disease may represent the potential protective autoimmune-evoking antigens.
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