Interphotoreceptor retinoid-binding protein derived peptide can induce experimental autoimmune uveoretinitis in various rat strains

Abstract

Experimental autoimmune uveoretinitis (EAU) is an intraocular inflammatory disease model induced by retinal specific antigens such as S-antigen and interphotoreceptor retinoid-binding protein (IRBP). The present study was aimed at testing the uveitogenicity of IRBP and an IRBP-derived peptide in various strains of rats with different RT1 (major histocompatibility complex in rats) haplotypes. Immunization with IRBP induced distinct EAU in LEW (RT1^l), WKAH (RT1^k), W/M (RT1^k), LEJ (RT1^j), and BUF (RT1^b) rats. IRBP also induced a low grade of EAU in SDJ (RT1^u), but no disease was detected in TO rats, another strain of the RT1^u haplotype. IRBP-derived peptide R16 (aa 1177–1191) induced severe EAU in LEW rats and moderate disease in the WKAH and W/M strains. Immunization with R16 also induced low levels of inflammation in eyes of 75% and 20% of LEJ and BUF rats, respectively, but this peptide did not cause any disease in SDJ and TO rats. Injection of Bordetella pertussis had minimum or no effect on the induction of EAU by peptide R16 in this study. These data thus indicate that peptide R16 can bind to various RT1 molecules in addition to RT1^l. Further, our observations support the notion that certain epitopes of IRBP could be uveitogenic in humans with different Hlα haplotypes.

Key Words:

• experimental autoimmune uveoretinitis (EAU)
• genetic control
• interphotoreceptor retinoid-binding protein (IRBP)
• major histocompatibility complex (MHC)
• RT1
• rat