角膜病是第二大致盲性眼病,炎症损伤是导致角膜盲的主要原因。我们前期发现NOD1存在于人类角膜，参与角膜炎症的形成，NOD1抑制剂Nodinhibit1能抑制和回退角膜新生血管、减轻炎症。最新研究结果显示NOD1可以通过激活MAKP信号转导通路参与炎症的形成。因此，我们推测Nodinhibit1可能依赖NOD1-MAPK信号转导通路来调控角膜炎症。我们拟通过NOD1-shRNA来调控NOD1表达，观察和分析沉默和过表达NOD1的角膜致炎细胞生物学功能变化；探讨RICK在RICK（NOD1下游基因）敲除鼠活体内和体外培养的角膜炎症细胞的作用，深入了解NOD1-MAKP信号转导通路在其中发挥的作用和机制；通过体内、外角膜炎症模型阐明Nodinhibit1作用的细胞类型、有效浓度及分子机制。研究为角膜炎症发生的分子机制提供新的研究思路，为设计合理的抗炎药物及寻找有效的抗炎靶点提供了理论基础。

The corneal inflammation is the main blinding cause of corneal disease,the incidence of which is secondary to the cataract. In our previous study, NOD1 has been found to be exclusively expressed in the cornea and participates in corneal neovascularization,NOD1 inhibitor Nodinhibit1 could reverse ocular alkaline burn-induced corneal neovascularization and supress inflammation. NOD1 has been recently detected to induce inflammation through MAPK singaling pathway in other tissues. Therefore, we speculated that whether Nodinhibit1 could suppress corneal inflammation through inactivating NOD1/MAKP signaling pathways. In this project, we will study the expression of NOD1 in cornea, and elucidate the role and mechanism of NOD1 in corneal inflammation through modulating the expression of NOD1 in cell and animal model. NOD1 silence in NICK-knockout mouse model will be performed to further confirm that NOD1 induces corneal inflammation. We will examine the role of Nodinhibit1 in corneal inflammation induced by NOD1/MAPK singaling pathway in vitro and in vivo. We expect to reveal the role and mechanism of NOD1-mediated corneal inflammation, and develop a new anti-inflammatory therapeutic compound.