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V. L. Perez, M. West, M. E. Raybourn, X. Yang, K. G. Shadrach, J. G. Hollyfield; Production of Anti-CEP Autoantibodies in Immune Mediated Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):202. doi: https://doi.org/.
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We have previously reported a novel murine model of immune mediated retinal degeneration induced by immunization with carboxyethylpyrrole (CEP)-modified albumin (CEP-MSA). CEP albumin adducts are generated in the retinal photoreceptors in response to oxidative stress and patients with age-related macular degeneration (AMD) have circulating CEP autoantibodies. The goal of this work is to test the role of anti-CEP antibody production in the generation of immune mediated retinal degeneration.
C57BL/6 were immunized in the footpad with CEP-MSA or non-adducted MSA emulsified in complete Freund’s adjuvant (CFA) followed with a subcutaneous challenge at day 10 with incomplete Freund’s adjuvant-CEP-MSA in the skin of the neck, followed by a second subcutaneous challenge two months later with CFA-MSA. Serum was collected at different time points and anti-CEP production was analyzed by ELISA. Specificity of anti-CEP autoantibody to retinal tissue was assessed by performing western blot analysis on retinal extracts and immunohistochemical staining using sera from immunized mice. Anti-CEP sera from immunized groups were also tested on human eye tissue from AMD and control individuals.
Anti-CEP-MSA autoantibody could be detected in immunized mice by day 30 after immunization and persisted for 12 months. A single band of approximately 40 kD was detected by western blot analysis of retinal extracts probed with sera form immunized mice. Immunohistochemical analysis demonstrates that the anti-CEP sera antibodies localized to scattered areas of the retinal pigment epithelium and photoreceptors. Moreover, anti-CEP serum binds to areas of drusen formation in the retina of human patients with AMD
Oxidative stress immune mediated retinal degeneration correlates with the production of autoantibodies against CEP modified protein. These antibodies recognize specific areas of the retina where the antigen is present and have the potential of mediating disease.
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