年龄相关性黄斑变性(Age-related macular degeneration，AMD)即将成为国内老年人致盲的首要病因，而诱发 AMD 的主要机制是氧化损伤。. 在模拟 AMD 发生环境的经典实验中，申请者发现 PAX2 表达水平显著降低； 过表达PAX2可增加细胞对氧化损伤的抵抗；下调则降低细胞的抵抗。提示 PAX2 可能参与了 AMD 的发生发展，但至今尚无 PAX2 在 AMD 相关方面的报道。. 基于以往的研究基础，本课题拟先从PAX2基因与蛋白两个层次着手，分析其调控网络，全局性了解 PAX2 的功能；然后在模拟 AMD 发生发展的细胞模型中，分析 PAX2 调控网络在氧化损伤前后的变化，找出氧化损伤的关键节点；最后在AMD患者的临床样品中验证这些关键节点的作用。. 本研究将为AMD的早期诊断、治疗或干预提供一定的分子依据。

Age-related macular degeneration is becoming the leading cause of blindness in elder people in China, and oxidative injury plays a main role in contributing to AMD.. In the classical experiments simulating AMD in vitro, applicant has found that the expression of PAX2 expression is down-regulated significantly. While over expression of PAX2 increases cells’ resistance to oxidative injury, low expression of PAX2 by shRNA reduces the resistance. Those data suggest PAX2 may involve in the development of AMD. Besides, there has been no report about the function of PAX2 in AMD pathogenesis so far. . Based on the applicant’s previous research, we first focus on the regulatory network of PAX2. We will study the function of PAX2 in all respects, including upstream cis-acting elements, trans-acting factors, protein complexes LncRNAs, the promoter location which PAX2 attach to and the downstream pathway of PAX2. Then, using three AMD pathogenesis models, we analysis the change of the PAX2 regulatory network before and after oxidative injury, trying to find out the checkpoint of oxidative injure. At last, we will confirm our results and double-check the function of PAX2 regulatory network in AMD patients.. This research will disclose the molecule mechanism of PAX2 in AMD pathogenesis, which will offer molecular evidence for AMD early diagnosis, treatment or intervention.