本课题组前期研究发现视网膜光损伤动物眼内1-磷酸鞘氨醇(S1P)水平升高，有研究发现淀粉样物质(Aβ)可经S1P介导炎性损伤导致Alzheimer发生，干性年龄相关性黄斑变性(dryAMD)玻璃膜疣中同样检测到Aβ表达。贯序上述理论，本研究旨在基于S1P通路探究Aβ在dryAMD中的作用。建立dryAMD细胞模型，通过抑制或增加细胞内S1P及Aβ分泌酶β-secretase的含量，观察干预前后Aβ前体蛋白(APP)及Aβ的生成情况，质谱测定S1P等相关鞘脂的含量变化，并由动物体内实验进一步验证；建立dryAMD细胞模型，经外源性Aβ及TNF-a干预，观察神经磷脂酶及神经鞘氨醇激酶活性，检查神经酰胺及S1P含量变化与下游炎症相关通路的相关性。通过上述研究，以期增加对dryAMD的认识，发现干预dryAMD的有效靶点，为dryAMD的防治提供新的科学依据。

Our preliminary experiments indicate that the level of sphingosine 1-phosphate has increased in the light-induced retinopathy animal eye. Several studies show that Amyloid-β can lead to Alzheimer via S1P pathway. Dry AMD, which has been also considered as neurodegeneration disease, express Aβ in its characteristic lesion-drusen too. Based on these theories, our study is aiming to explore the role of Aβ in dry AMD. Using type I collagen membrane, MMP-2, and human ARPE-19 cell to establish dry AMD cell model. Endogenously inhibit or exogenously increase S1P and Aβ-secretase, and then detect the amount change of Amyloid precursor protein (APP), Aβ, and related sphingolipids, including S1P. Verify the result from in vivo experiment. Establish dry AMD cell model, and interfere with exogenous Aβ and TNF-a. Observe the activity of SMase and Sphingosine kinase. Check the correlation between the amount change of ceramide, S1P and the downstream inflammation factors. Revealing the possible pro-inflammation mechanism of ARPE-19. Based on above studies, we are hoping to increase our understanding of dry AMD, finding the target spot, and providing scientific support for the diagnosis and treatment of dry AMD.