干性年龄相关性黄斑变性（Dry AMD）是由于视网膜色素上皮细胞（RPE）退化并死亡导致中央视力下降及致盲的眼病，目前缺乏有效的治疗措施及药物。申请人前期通过高通量测序发现在蓝光诱导负载A2E的ARPE-19细胞凋亡的干性AMD模型中ZFAND2A基因表达显著上调，且ZFAND2A启动子区组蛋白H3K4me3分布增加，但其具体作用分子机制尚不明确。本研究拟从细胞、动物、分子水平阐明ARPE-19细胞凋亡中组蛋白H3K4甲基化酶MLL1对ZFAND2A基因表达调控的分子机制；利用Zfand2a-/-小鼠验证Zfand2a对蓝光诱导视网膜损伤的影响；研究有效抑制ZFAND2A基因表达的天然产物金丝桃苷保护ARPE-19细胞凋亡的作用机制，为防治干性AMD提供潜在药物作用靶点，为利用其分子机制研发干性AMD的靶向药物提供理论依据。

Dry age-related macular degeneration (AMD) is a kind of progressive blinding disease primarily due to dysfunction and loss of the retinal pigment epithelium (RPE) of the eye. Currently, there is no effective treatment for dry AMD. In our preliminary experiments, we have first found that the expression of ZFAND2A was significantly increased and higher levels of H3K4me3 at promoter region of ZFAND2A compare with controls in blue light irradiation of A2E-laden ARPE-19 cells. Therefore, the project aims to find out the molecular mechanism of regulation of ZFAND2A gene expression by histone H3K4 methyltransferase MLL1 via a series of biological technologies; and the role of Zfand2a on blue light induced retinal damage in Zfand2a knockout mice; and investigate the molecular mechanism for hyperoside through it’s inhibitory effect on the expression of ZFAND2A. Above all, we will elucidate the molecular mechanism of ZFAND2A in the apoptosis of ARPE-19 cells, and provide potential drug target for prevention and therapy of dry AMD. Furthermore, the molecular mechanism is used to provide a theoretical basis for development of targeted therapy drugs for dry AMD.