Su Yuhan, Tao Tianyu, Liu Xiuxing, Su Wenru
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China; Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
Biochem Pharmacol. 2022 Oct;204:115236. doi: 10.1016/j.bcp.2022.115236. Epub 2022 Aug 27.
Non-infectious uveitis (NIU) refers to various intraocular inflammatory disorders responsible for severe visual loss. Cytokines participate in the regulation of ocular homeostasis and NIU pathological processes. Cytokine receptors transmit signals by activating Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. Increasing evidence from human NIU and experimental models reveals the involvement of the JAK-STAT signaling pathway in NIU pathogenesis. Several small-molecule drugs that potentially inhibit multiple cytokine-dependent pathways are under investigation for treating autoimmune diseases, implicating possible applications for NIU treatment. This review summarizes the current understanding of the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and NIU pathology, providing a rationale for targeting JAKs and STATs for NIU treatment. Moreover, available evidence for the safety and efficacy of JAK inhibitors for refractory uveitis and potential approaches for treatment optimization are discussed.
非感染性葡萄膜炎（NIU）指的是导致严重视力丧失的各种眼内炎症性疾病。细胞因子参与眼部内环境稳态和NIU病理过程的调节。细胞因子受体通过激活Janus激酶（JAK）和信号转导及转录激活因子（STAT）蛋白来传递信号。来自人类NIU和实验模型的越来越多的证据表明JAK-STAT信号通路参与NIU的发病机制。几种可能抑制多种细胞因子依赖性途径的小分子药物正在研究用于治疗自身免疫性疾病，这暗示了其在NIU治疗中的可能应用。本综述总结了目前对JAK-STAT信号通路在眼部内环境稳态和NIU病理学中不同作用的理解，为将JAK和STAT作为NIU治疗靶点提供了理论依据。此外，还讨论了JAK抑制剂治疗难治性葡萄膜炎的安全性和有效性的现有证据以及治疗优化的潜在方法。
