年龄相关性黄斑变性(AMD)是如今导致中老年人严重视力丧失最主要的原因。而以视网膜色素上皮(RPE)细胞功能障碍和死亡为特征的干性AMD是AMD最常见的一种类型，目前还没有有效的治疗方法。研究表明铁离子在干性AMD的发生发展中是一个重要的氧化应激产生源头，而铁死亡可能是氧化应激介导的RPE细胞死亡的主要方式。前期研究提示丹参中的主要活性成分丹参酸A(SAA)能明显改善铁超载小鼠的视网膜损伤并降低RPE细胞内铁沉积。该项目将通过阐明SAA对RPE细胞铁死亡的保护机制探讨SAA对干性AMD的治疗作用。主要研究内容包括以hepcidin基因敲除小鼠为干性AMD模型研究SAA对视网膜的保护作用；以Erastin诱导原代RPE细胞铁死亡，从铁代谢和丝裂原活化蛋白激酶(MAPKs)通路研究SAA对RPE细胞铁死亡的保护机制。该项目将对了解RPE细胞铁死亡在干性AMD中的作用及药物作用靶点有重要意义。

Age-related macular degeneration (AMD) is the primary cause of severe vision loss in the elderly. The most common type, atrophic AMD, is characterized by retinal pigment epithelial (RPE) cell dysfunction and death, and it has no effective treatment. Research shows that iron is an important source of oxidative stress during the development of atrophic AMD and that ferroptosis might be the primary means by which RPE cell death is mediated by this stress. Previous studies suggest that SAA, the primary active ingredient in Salvia miltiorrhiza, could improve retinal injuries in iron-overload model mice and reduce iron deposition in RPE cells. In this project, we explored the therapeutic effects of salvianic acid A (SAA) on atrophic AMD by clarifying its protective mechanism against the ferroptosis of primary RPE cells through the iron metabolism and mitogen-activated protein kinases (MAPKs) pathways. Hepcidin knockout mice were used as the atrophic AMD model, and erastin was used to induce ferroptosis. This project will be of great significance in the effort to understand how ferroptosis of RPE cells plays a role in atrophic AMD and in determining the target of drug action.