Uveitopathogenic site of the gamma-subunit of cyclic guanosine monophosphate phosphodiesterase in Lewis rats.

PURPOSE The gamma-subunit of cyclic guanosine monophosphate phosphodiesterase (PDEgamma) plays an important role in the phototransduction process of rod photoreceptors. A previous report indicated that experimental autoimmune uveoretinitis (EAU) could be induced in Lewis rats by immunization with PDEgamma. In this study, we identified the uveitopathogenic site of PDEgamma synthetic peptides and identified pivotal amino acid residues using analogue peptides. METHODS Several synthetic peptides derived from PDEgamma plus adjuvants were injected in Lewis rats. The induction of EAU was examined clinically and histologically. In addition, humoral and cellular immunity against peptides was investigated. RESULTS The smallest uveitopathogenic peptide was identified as PDEgamma 64-76 (ITVICPWEAFNHL), which consists of 13 amino acid residues, and the core sequence was identified as PDEgamma 70-76 (WEAFNHL), which consists of 7 amino acid residues. The lowest dose of peptide to induce EAU was 0.03 nmol. The pivotal amino acid residues for eliciting EAU are at 70(W), 71(E), 73(F), and 75(H). CONCLUSION Our findings demonstrated the presence of a potent uveitopathogenic site in PDEgamma whose potency in Lewis rats was comparable to that of interphotoreceptor retinoid-binding protein.