Evaluation of the effectiveness and reliability of tofacitinib treatment on the management of uveitis symptoms in an experimental model of posterior uveitis

Non-infectious uveitis (NIU) is a disease, which can cause severe vision loss due to inflammation when left untreated. Therefore, experimental models are essential for new treatment alternatives. In the present study, it was aimed to create an experimental uveitis model induced by retinal S-antigen (RSA), which causes panuveitis that is similar to NIU and plays an important role in the pathophysiology of Behcet uveitis (BU), and to investigate the efficacy and reliability of oral use of small molecule inhibitor tofacitinib in this model. The subjects consisted of 19 Wistar rats. Fifteen rats were immunized by subcutaneous administration of 15 μg / rat RSA and divided into 3 groups (healthy control / sham control / treatment group) with five subjects in each uveitis group. Two rats were included in the healthy control group, and the remaining 2 rats were given only tofacitinib to test the safety of tofacitinib, and retinal sections were examined histologically at the end of the experiment. Uveitis formation and tofacitinib activity were confirmed by the determination of cytokine levels by ELISA test in blood taken directly from the heart. It has been observed to develop 100% uveitis with clinical and histological score in Wistar rats (p<0.001). Oral tofacitinib treatment was also determined to delay the onset of clinical uveitis findings and decrease the clinical and histological score, however the decrease in histological score was not at the expected level (p values; 0.393, 0.089). Tofacitinib treatment was discovered to suppress inflammation by decreasing cytokine levels, primarily in IL-17 (p = 0.023). Tofacitinib can be an effective and reliable alternative in the treatment of BU. Keywords: Experimental Autoimmune Uveitis, Behçet uveitis, Wistar rat, IL-6, IL- 10, IL-15, IL-17, IL-23, IFNγ, Tofacitinib.