Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU)

Abstract

Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation.