脉络膜巨噬细胞(CMø)分泌的促炎因子和VEGF诱导脉络膜新生血管(CNV)形成，参与新生血管性年龄相关性黄斑变性(nAMD)的发病。NLRP3是巨噬细胞促炎作用的关键组分，我们前期研究发现，特异性NLRP3新型小分子抑制剂IFM，能有效抑制炎性复合体活化，在nAMD中保护RPE细胞形态结构。然而IFM在nAMD中的作用尚不清楚。本课题借助多模态影像学观察IFM对nAMD表型的影响，利用巨噬细胞NLRP3 KO和NLRP3体内研究工具ASC-Citrine荧光小鼠初步探讨IFM通过NLRP3调控CMø发挥抑制炎症反应和VEGF分泌的作用；再深入研究IFM通过NLRP3/Caspase-1通路，一方面抑制IL-1β分泌和M1型巨噬细胞极化；另一方面直接或经IL-1β间接调控转录因子GATA-4，共同抑制VEGF分泌的机制；最后收集临床标本验证上述发现，以期为nAMD的防治提供新的干预靶点。

The choroidal macrophages (CMø) secret proinflammatory cytokines and VEGF inducing the formation of choroidal neovascularization (CNV). It plays vital role in the development of neovascular age-related macular degeneration (nAMD). NLRP3 is the key component of the inflammation in macrophages. We previously found that the NLRP3 specific novel small molecular inhibitor IFM reduced the activation of inflammasome in AMD, thus protected the morphology of RPE cells. However, the role of IFM in nAMD is still unknown. In this study, firstly we will make use of the multimodal imaging to observe the consistent changes of the nAMD phenotype with IFM treatment. Secondly, the conditional macrophage NLRP3 knock out mouse and ASC-Citrine mouse model will be applied in our study to investigate that IFM inhibits the NLRP3 inflammation and VEGF secretion through CMø. Next, we will further explore that on one hand IFM inhibits the secretion of IL-1β and M1 polarization through the NLRP3/Caspase-1 pathway, on the other hand IFM regulates transcription factor GATA-4 direct or undirect through IL-1β, thus inhibit the VEGF expression. In the end, we will collect the PBMC and intraocular fluid from clinical patients to verify the above findings, and provide new therapeutic strategy for the prevention and treatment of nAMD.