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Biying Xu, Xiuzhi Jia, Jihong Tang, Rachel R Caspi, Igal Gery; Laquinimod effectively inhibits development of EAU and its associated immune effector responses. Invest. Ophthalmol. Vis. Sci. 2019;60(9):792.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental autoimmune uveitis (EAU), an animal model for human uveitis, serves as a platform for testing potential therapeutic compounds. Here, we tested the efficacy of laquinimod (LAQ), previously shown to be an aryl hydrocarbon receptor antagonist, to suppress EAU and related immune responses.
EAU was induced in C57BL/6J mice by immunization with 300ug of IRBP peptide p651-670, in CFA. LAQ, provided by TEVA, at a dose of 25mg/Kg, or PBS for control, were administered daily by oral gavage. Mice were treated either from day 0 or day 7 post immunization (prevention and reversal regimens, respectively). EAU progression was monitored by fundoscopy and confirmed by histology. Immune responses to p651-670 were assessed by antigen specific proliferation and production of IFN-gamma and IL-17, which were measured by ELISA or intracellular cytokine staining and flow cytometry. FoxP3 expression by CD4+ lymphocytes was determined by flow cytometry. Two-tailed Student's t-test and two-way ANOVA were used for statistical analysis.
Treatment with LAQ from day 0 completely inhibited EAU induction and the associated proliferative and cytokine responses to p651-670, both by ELISA and by intracellular staining. Mice treated with LAQ from day 7 developed reduced EAU and related immune responses. Although responses in mice treated with LAQ from day 7 were only partially suppressed, in all assays responses of the treated mice were significantly below their controls. Treatment with LAQ increased slightly the proportion of FoxP3+ cells in the spleen and draining lymph nodes, and significantly elevated the proportion of Foxp3+ T cells in inflamed eyes.
Prevention treatment with LAQ completely inhibited the induction of EAU and its associated immune effector responses. Further, even reversal treatment regimen (starting on day 7 post immunization) significantly suppressed these responses and lowered EAU scores.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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