This project was initiated in FY 2006, as a component of project EY000069-29. This project is aimed at analyzing the capacity of two synthetic copolymers, Copaxone (also known as Glatiramer Acetate) and the experimental new molecule designated YFAK, to inhibit immune-mediated ocular inflammation. Copaxone is currently in use for treatment of multiple sclerosis and was found in our previous study (Zhang et al., J. Neuroimmunol., 2000, 103:189) to inhibit development of experimental autoimmune uveitis (EAU). The extension of the project in FY 2007 yielded the following new information concerning the activities of the two copolymers:? ? (i) Both copolymers inhibited EAU development in mice when administered together with the immunizing antigens, interphotoreceptor retinoid-binding protein (IRBP), or peptide 161-180 from the sequence of this molecule. Whole IRBP was used for EAU induction in B10.A mice, whereas peptide 161-180 was used with the B10.RIII mice. The two copolymers inhibited the disease in B10.RIII more efficiently than in B10,A and in both experimental systems YFAK was substantially more effective than Copaxone.? ? (ii) Our previous studies (EY000069-29, FY 2006) attributed the copolymers inhibitory effect in part to the capacity of the copolymers to compete with the uveitogenic antigen for the combining sites on the major histocompatibility complex (MHC) molecules on antigen presenting cells. In addition, we found in FY 2007 that the copolymers affect immune responses also by inducing the development of regulatory T-cells. Cell lines specific against either Copaxone or YFAK were found immunosuppressive, capable of inhibiting development of EAU in mice, as well as suppressing proliferative responses of lymphocytes in culture. In both assays, the line cells specific against YFAK were much more suppressive than those specific to Copaxone. Both cell lines exhibited cytokine production profile of the Th2 type, with the YFAK line being superior to the Copaxone line in the released cytokine levels.
| Yin, Hongen; Vistica, Barbara P; Chan, Chi-Chao et al. (2009) Inhibition of experimental autoimmune uveitis by amino acid copolymers. J Neuroimmunol 215:43-8 |
