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DI Ham, S Gentleman, CC Chan, JH McDowell, TM Redmond, I Gery; High Uveitogenicity of RPE65 in Rats . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1541.
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Purpose:RPE65, a protein that plays a pivotal role in the visual process, is specific to the retinal pigment epithelium. This study examined the uveitogenicity of this molecule in rats. Methods:Rats of four inbred strains (Lewis, Brown Norway, Fischer, SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund's adjuvant, and treated concurrently with killed Bordetella pertussis bacteria, as indicated. Development of inflammatory disease was examined both clinically and histologically. Results:Lewis rats immunized with RPE65 developed acute and severe inflammatory eye disease that affected most ocular tissues on day 8-15 post-immunization. Both native and recombinant bovine RPE65 were active in this system. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag, i.e., 1 microgram per rat, but the inflammatory changes induced by RPE65 at higher dose ranges (30-100 microgram per rat) were less severe than those induced by S-Ag at comparable doses. Concurrent treatment of the RPE65-immunized rats with Bordetella pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. The pathology of RPE65-induced ocular inflammation was characterized by marked pars planitis and occasionally Dalen-Fuchs nodule-like lesions in addition to the uveoretinitis commonly seen in S-Ag induced EAU. Fischer rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway rats developed severe disease when immunized with RPE65, but responded poorly to S-Ag. SHR rats were essentially resistant to disease induced by both proteins. Conclusion:RPE65 is highly uveitogenic in rats, thus providing a new animal model for uveitis and suggesting that this molecule could be involved in pathogenic autoimmunity in the eye.
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