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Gerhild Wildner, Maria Diedrichs-Möhring, Ulrike Kaufmann, Christine von Toerne, Stephan R Thurau; Immune mechanisms underlying relapsing-remitting or monophasic experimental autoimmune uveitis (EAU) with neovascularization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):528.
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© ARVO (1962-2015); The Authors (2016-present)
We investigated spontaneously relapsing-remitting EAU, induced with the interphotoreceptor retinoid-binding protein peptide R14 or monophasic/chronic disease with chorioretinal neovascularization induced with retinal S-Antigen peptide PDSAg to elucidate immune mechanisms underlying the different disease courses.
Lewis rats were immunized with peptide PDSAg or R14 or both to induce EAU and to generate T cell lines. T cell lines were analyzed for gene and protein expression/secretion. Rats with EAU induced by both antigens were treated with chemokine mutants, analyzed for intraocular T cell populations or injected intraocularly with antibodies to IFN-g, IL-17 and IL-10 to investigate the effect on EAU.
Gene expression analysis revealed 26 genes upregulated in R14-specific T cells upstream or downstream of IFN-g and belonging to various intracellular signaling pathways. PDSAg-specific T cells produced more IL-17, IL-6, IL-10, CCL2 and VEGF (resulting in CNV) than R14-specific T cells, which had higher secretion of IFN-g, IL-18, CCL3 and CCL5. R14-induced relapsing EAU was significantly ameliorated by intraocular injection of anti-IFN-g and anti-IL-10 and deteriorated by anti-IL-17. PDSAg-induced, monophasic EAU was only reduced with anti-IL-17. Cells co-expressing IFN-g, IL-17 and IL-10 increased during monophasic and decreased during relapsing disease, Foxp3-expression increased late in monophasic EAU. A CCL5-mutant only suppressed PDSAg-, but not R14-mediated EAU, and co-immunization of rats with both antigens revealed that the monophasic EAU dominated with respect of the disease course and intraocular T cell populations.
The two EAU models in Lewis rats will help us to understand the interplay of various immune mechanisms in relapsing autoimmunity and to develop and test new therapies for uveitis in ongoing disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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