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Elodie Bousquet, Serge Camelo, Jocelyne Annat, Francine Behar-Cohen, Yvonne de Kozak; Protective effect Of Intravitreal Administration Of Tresperimus, An Immunosuppressive Drug, On Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6582.
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© ARVO (1962-2015); The Authors (2016-present)
To test the efficiency of Tresperimus, animmunosuppressive drug, in experimental autoimmune uveoretinitis (EAU).
EAU was induced in Lewis rats by S-Ag immunization. Three intravitreal injections of Tresperimus were performed during the afferent phase of EAU. Pharmacokinetics of Tresperimus was performed in ocular tissues and plasma. Ocular disease severity was graded by clinical, histological and immunohistochemistry analysis. Blood ocular barrier permeability was evaluated by protein concentration in ocular fluids. The activation of macrophages was checked by in vitro treatment. Immune response to S-Ag was examined by delayed type hypersensitivity (DTH), titration of inflammatory cytokines in lymph nodes and in infiltrated cells in ocular fluids by RT-PCR and in ocular fluids by multiplex ELISA.
Tresperimus could be detected in the ocular milieu up to 8 days following last injection but was not detectable in plasma of treated rats. Tresperimus treatment protected against retinal damages with reduction of blood ocular barrier permeability breakdown. Tresperimus suppressed the expression of NOS-2 and reduced NF-ΚBp65 nuclear expression in ocular macrophages suggesting a change of their phenotype. Further, in vitro it significantly reduced production of CCL-3 by macrophages, and in vivo the intraocular concentration of the T cell cytokines IL-2, IL-17, but increased that of IL-18. By contrast, in inguinal lymph nodes draining the immunization site, Tresperimus treatment did not modify the level of IL-2, IL-17. Moreover, DTH to S-Ag was not different in control and treated rats. Altogether, the treatment did not modify the systemic T cell reactivity to S-Ag.
Intraocular Tresperimus treatment regulated macrophage activation and reduced Th-17 T cell mediated response in the eye with no modification of the systemic immune response.
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