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H. Yin, B.P. Vistica, C.–C. Chan, E.F. Wawrousek, I. Gery; Modulation of Immune–Mediated Ocular Inflammation by Copolymers . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4547.
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© ARVO (1962-2015); The Authors (2016-present)
Copaxone, also known as Copolymer 1, or Glatiramer acetate, suppresses EAE and is an effective treatment for MS. We previously reported (Zhang et al., J. Neuroimmunol., 103:189, 2000) that Copaxone also inhibits partially the development of EAU in B10.A mice. The present study is aimed at extending the investigation of Copaxone’s effect on immune–mediated ocular inflammation, as well as testing the effects of newly introduced copolymers, shown to be superior to Copaxone in inhibiting EAE (Stern et al., PNAS, 101:11743, 2004).
Copaxone was a gift from TEVA, whereas the copolymer YFAK was provided by Peptimmune. EAU was induced in B10.RIII mice by immunization with IRBP peptide 161–180, 10 µg/mouse, emulsified in CFA, whereas B10.A mice were immunized with whole bovine IRBP, 50 µg/mouse, in CFA, along with pertussis toxin, 0.5 µg. Copaxone treatment, 0.5 mg/mouse was incorporated in the CFA emulsion. The disease was assessed by both clinical and histological examinations. Ocular inflammation adoptively transferred with Th1 cells was carried out and assessed as detailed in Kim et al., IOVS, 43:758, 2002. Recipients were irradiated with 450 Rad, injected with 100,000 Th1 cells and treated with Copaxone 0.5 mg/mouse or PBS on days 0, 2, 4 and 6.
Development of EAU in B10.RIII mice was completely suppressed by Copaxone. On the other hand, only partial inhibition of disease was observed in most Copaxone–treated B10.A mice. Interestingly, unlike the inhibition of EAU, treatment of B10.RIII mice with Copaxone had no effect on the lymphocyte response of these mice to PPD, and partially inhibited the response to IRBP 161–180. Copaxone also inhibited ocular inflammation adoptively transferred with Th1 cells. In addition, we are currently examining the immunosuppressive activity of the copolymer YFAK, as compared to that of Copaxone in the various experimental systems of this study. The data will be presented at the meeting.
The eye is the first non–CNS organ in which immune–mediated inflammation is inhibited by Copaxone, and the data in this study thus underscore the non–organ specificity of this immunosuppressive copolymer. Further, there is no similarity between Copaxone and ocular antigens and its effect in the systems used here supports the notion that the compound acts by promoting immunoregulation. Our data suggest that Copaxone, a non–toxic compound could be used for treatment of immune–mediated eye conditions.
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