葡萄膜炎是主要致盲性眼病之一，目前所用药物不良反应较多，亟需探索新的眼特异的抗炎制剂。已有证据表明Toll样受体固有免疫通路通过调节机体自身免疫在葡萄膜炎的发生发展中发挥重要作用，但TBK1介导的固有免疫识别通路在葡萄膜炎中的作用与机制尚未明确。TBK1通路在识别外源或细胞自身泄漏的核酸等信号后，能够强烈激活机体的固有免疫反应，生成多种促炎因子与抗炎因子并调节免疫细胞的分化与功能。同时，为拓展葡萄膜炎的研究工具，充分利用各种模型的优势，本项目前期已成功建立具有特色的脊椎动物斑马鱼葡萄膜炎模型，并已获得了数个相关基因敲除的斑马鱼鱼系。在此基础上，拟进一步探索TBK1介导的固有免疫识别通路在葡萄膜炎发生发展中的功能和作用机制，并开发可用于高通量药物筛选的斑马鱼葡萄膜炎模型。本研究具有重要的生物学意义和潜在的临床转化价值，对进一步明确葡萄膜炎的发病机制及筛选潜在的特异性药物都具有重要的价值。

Uveitis is a worldwide leading cause of vision impairment and blindness. However, the efficiency of current therapy is limited and often arises serious side effect, it thereby requires urgently an effective and specific medicine. It has documented that innate immune through Toll-like receptor signaling played a crucial role in the development of uveitis via the regulation of autoimmune response. While the TBK1-mediated signaling of cytosolic nucleic acid sensing by RIG-I-like receptors and cGAS is a fast-developed research area in recent years, its function and mechanism in uveitis is largely unexplored. On the other hand, we have developed a uveitis model based on zebrafish and established a few knockout lines for key components of TBK1 signaling pathway, which provides us advantages over conventional uveitis model on rat and set us a strong basis for proposed study. By combination of mammalian primary/cultured cells and zebrafish model, we plan to define the key role of TBK1 mediated cytosolic nucleic acid sensing and uncover the mechanism in uveitis development. Besides, we will establish a high-throughput screening for chemical compounds on zebrafish model, to seek the lead compounds for the potential cure of uveitis. Therefore, the proposed study will not only unravel the complex mechanism for uveitis development, but might also benefit directly to our eye health.