ANALYSIS OF UVEITOGENIC SITES IN PHOSDUCIN MOLECULE

Purpose. Phosducin, a retinal photoreceptor protein, induces experimen tal autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptide s. Methods. Antigen peptides were synthesized according to the amino a cid sequence of the rat-derived phosducin with a peptide-synthesizer a nd purified by reversed-phase HPLC. First, 13 peptides covering the en tire sequence of phosducin were synthesized, and each was injected int o the hind footpad of Lewis rats for immunization, and induction of EA U was examined clinically and histologically. Next, peptides that appe ared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. Results. Of the 13 pepti des used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior cha mber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and ser ous retinal detachment was found in cases of severe inflammation. Infi ltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino aci d sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunize d with these peptides also exhibited high value on lymphocyte prolifer ation assay. Conclusion. Phosducin has 5 uveitogenic sites. Among othe rs, one of them has potent and others weak uveitogenicity.