玻璃膜疣是年龄相关性黄斑变性（AMD）的早期体征，其中富含脂肪酸和脂蛋白。研究表明HTRA1启动子区域rsll200638发生G→A变异时会使人群患AMD风险显著提升，该变异会导致HTRA1在AMD患者视网膜色素上皮（RPE）和玻璃膜疣中高表达，但是HTRA1在玻璃膜疣形成过程中的作用尚不清楚。我们前期实验结果显示HTRA1在RPE细胞中高表达会抑制细胞对外源脂质分子的摄入和细胞中脂质分子外排，造成脂滴在细胞中累积，引起RPE细胞死亡。因此，我们提出HTRA1能否通过调控RPE细胞的脂质代谢来介导玻璃膜疣的形成？本项目拟采用腺病毒及腺相关病毒、短发夹RNA、基因工程小鼠和脂肪酸合成酶激动剂及抑制剂等工具，通过激光共聚焦、细胞能量代谢、蛋白印迹和实时荧光定量PCR等方法，揭示HTRA1调控RPE细胞脂质代谢介导玻璃膜疣形成的分子机制，为AMD的早期诊断和治疗提供新的科学依据和实践基础。

Drusen in the macula is a common early sign of age-related macular degeneration (AMD) ，which is rich in long-chain fatty acids and lipoproteins. Studies have shown that the G→A variation of the single nucleotide polymorphism site rsll200638 in the HTRA1 promoter region significantly increases the risk of AMD in the population, and this variation will lead to high expression of HTRA1 protein in AMD patients’ RPE and drusen. However, the role of HTRA1 in the drusen formation is still unclear. Our previous experimental results showed that overexpression of HTRA1 in RPE cells inhibited the uptake of exogenous fatty acids and the efflux of lipid molecules in the cells, resulting in the accumulation of lipid droplets in the cells, which caused the death of RPE cells. Therefore we propose the hypothesis that HTRA1 may mediate the drusen formation in AMD through regulating lipid metabolism in RPE cells.With adenovirus and adeno-associated virus, short hairpin RNA, genetically engineered mice, fatty acid synthase agonists and inhibitors, this project try to reveal the mechanism of HTRA1 regulating lipid metabolism in RPE cells to mediate drusen formation in AMD by laser confocal, cell energy metabolism, western blotting and real-time quantitative PCR. The study will provide new scientific clues and experimental basis for the early diagnosis and treatment of AMD.