New therapeutic approaches in uveitis

Purpose Autoimmune uveitis is a severe disease, responsible for approximately 10% of acquired blindness. The side effects induced by systemic steroids or immunosuppressive therapies have prompted us to search for more specific treatments. Recently, tyrosine kinase inhibitors, including imatinib and sunitinib, have shown interesting properties in several autoimmune diseases. Their immunomodulating properties make them potential interest in the treatment of autoimmune uveitis and we analyzed their therapeutic effects in the mouse model of experimental autoimmune uveitis. Methods We induced uveitis to C57BL6 mice by immunization with IRBP protein, and we performed a randomized blinded controlled trial in 30 mice treated with either sunitinib (50mg/kg/day), imatinib (50mg/kg/day) or placebo. We then compared the efficiency of these treatments by measuring the frequency and the severity of the uveitis induced. Results An effect 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 that sunitinib efficiency is most likely related to the immunomodulation of the immune response, with a reduction in the Th17 response and an inhibition of T cell proliferation. Conclusion Thus, we report for the first time that a tyrosine kinase inhibitor can prevent experimental autoimmune uveitis or decrease its intensity. In particular, sunitinib could be considered as a potential treatment for autoimmune uveitis.