Uveitopathogenic Site of the γ-Subunit of Cyclic Guanosine Monophosphate Phosphodiesterase in Lewis Rats

Purpose: The γ-subunit of cyclic guanosine monophosphate phosphodiesterase (PDEγ) 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 PDEγ. In this study, we identified the uveitopathogenic site of PDEγ synthetic peptides and identified pivotal amino acid residues using analogue peptides. Methods: Several synthetic peptides derived from PDEγ 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 PDEγ 64-76 (ITVICPWEAFNHL), which consists of 13 amino acid residues, and the core sequence was identified as PDEγ 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 PDEγ whose potency in Lewis rats was comparable to that of interphotoreceptor retinoid-binding protein.