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YICHEN XIAO, Wenru Su; Tofacitinibhas preventive and therapeutic effects for uveitis in mice model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):793. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the roles of tofacitinib in the treatment of uveitis and the underlying mechanisms.
The first group of experimental autoimmune uveitis (EAU) mice were intraperitoneally injected with different dose of Tofacitinib (30 mg/kg,10mg/kg,5mg/kg) on alternate days, from the day of the induced immunization until euthanasia on postoperative day(day 28). The second group of EAU mice were treated with the exact same way after the onset of uveitis(day 14 to day 28). The clinical signs of the uveitis were evaluated and recorded according to a previously published system. Proinflammatory cytokines expression in serum were detected by histology, real-time PCR, and western blot. The Th17/Treg balance and other subtypes lymb cells are tested by the mechanisms of action of tofacitinib in vitro.
In comparison with the control group, treatment with tofacitinib significantly prevents uveitis from happening in EAU mice. Moreover, tofaticinib treatment alleviated fundus inflammation in vivo and in vitro,as characterized by downregulated CD4(+) IFN-γ(+) IL17(+) TNF(+)cells frequency,upregulated CD4(+) Foxp3(+) cells frequency,and related RNA levels of pro-inflammatory mediators. It reduced serum levels of other proinflammatory cytokines and interferon responses in splenocytes and lymph gland tissue.
Our results demonstrate that tofacitinib, a JAK inhibitor approved by FDA, plays a positive role in prevention and teatment in EAU mice. These findings indicate that tofaticinib might be a potential alternative treatment for uveitis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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