M2型巨噬细胞极化是促进脉络膜新生血管（CNV）发生发展的重要病理机制之一，确切分子机制不明。既往发现脂代谢参与M2型巨噬细胞极化过程。申请人前期研究发现核受体转录共抑制因子NCoR1是调节脂代谢途径上游关键分子。新近研究发现巨噬细胞特异性敲除NCoR1小鼠经激光损伤眼底建模后，CNV明显变小，伴有M2型巨噬细胞数量显著减少。本课题以上述研究发现为基础，拟采用CNV体内小鼠模型和原代巨噬细胞体外诱导分化模型，通过转录组学、脂质组学、ChIP等方法深入研究NCoR1调控巨噬细胞脂代谢的分子机制，以及NCoR1下游脂代谢基因在巨噬细胞极化和CNV中的作用及分子机制。通过上述研究，将明确NCoR1调控脂代谢途径促进M2型巨噬细胞极化和CNV发生发展的分子机制。课题的完成将极大丰富CNV发生发展机制及理论，为深入了解湿性AMD病理分子机制和发现潜在的有效的治疗靶点提供理论基础和科学依据。

M2 polarization of macrophages is an important factor in the development of choroidal neovascularization (CNV), but the molecular mechanism is still unclear. It has been previously discovered that lipid metabolism is involved in the M2 polarization of macrophages. Our previous study revealed that NCoR1 is a key regulator in lipid metabolism. Moreover, macrophage-specific knockout NCoR1 mice were more able to inhibit CNV in a laser-induced CNV mouse model, accompanied by a significant decrease in the number of M2 macrophages. Based on this, we will further study the role and molecular mechanism of NCoR1 in the regulation of lipid metabolism, macrophage polarization and CNV development through transcriptomics, lipidomics, ChIP and so on. Through the above studies, it is clear that NCoR1 regulates lipid metabolism to promote M2 macrophage polarization and the development of CNV. The completion of this project will greatly enrich the mechanism of CNV development, and provide theoretical basis and scientific grounds for understanding the molecular mechanism of wet AMD pathology and discovering potential therapeutic targets.