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Narjisse M. Feraoun, Aurelie Hesbert, Antoine Brezin, Dominique Monnet, Frederic Batteux; New Therapeutic Approaches in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3225.
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Autoimmune uveitis is a severe disease, responsible for approximately 10% of acquired blindness on adults. Systemic corticosteroid or immunosuppressive therapy have heavy side effects, which leads to seek for more targeted alternatives, based on an immunomodulation of the response rather than immunosuppression. Recently, tyrosine kinase inhibitors, including imatinib and sunitinib, have shown interesting properties in several autoimmune diseases. Their immunomodulation properties make them potential interest in the treatment of autoimmune uveitis. In this study, we analyzed the therapeutic effects of these promising compounds in the mouse model of experimental autoimmune uveitis.
We induced uveitis to C57BL6 mouse strains by immunization with IRBP protein, and we performed a randomized blinded controlled trial where 30 mice were treated with either sunitinib (50mg/kg/day), imatinib (50mg/kg/day) or placebo. We then compared efficiency of these treatments by measuring the number and the severity of induced uveitis.
An efficiency of sunitinib in the prevention of experimental autoimmune uveitis was observed, with an average uveitis clinical score of 1.1 in the control group, 0.70 in the imatinib group (p=0.28) and 0.36 in the sunitinib group (p=0.02). This effect was confirmed by retina histological examination, with a histopathological score of 0.95 in the control group versus 0.19 (p=0.003) in the sunitinib group. We furthermore demontrasted, by analyzing the immune response in the different groups, that sunitinib efficiency is most likely due to immune response modulation, with a reduction of Th17 response and an inhibition of T cells proliferation.
To our knowledge, we thus reported the first evidences of a tyrosine kinase inhibitor effect for prevention of frequency and intensity of uveitis in a mouse model of experimental autoimmune uveitis. In particular, sunitinib may constitute an interesting new treatment for autoimmune uveitis.
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