FTY720是鞘氨醇结构类似物，具有独特的免疫抑制作用，但其作用是否仅仅局限于免疫抑制目前存在争论。新的研究发现FTY720能抑制神经酰胺合成酶进而减少神经酰胺的产生。视网膜光损伤的基本病理改变是感光细胞凋亡。研究表明减少神经酰胺能阻止感光细胞凋亡。.我们初步研究发现：1）在光损伤中，视网膜神经酰胺显著升高；2）FTY720能保护视网膜光损伤；3）该保护不依赖于对外周血淋巴细胞的抑制。故我们推测：在光损伤中，FTY720的免疫抑制可能没有参与对视网膜的保护；FTY720可能通过抑制神经酰胺合成酶，减少神经酰胺而阻滞感光细胞凋亡。.我们拟在现有基础上研究：1）FTY720对视网膜神经酰胺代谢及关键酶（基因/蛋白表达,酶活性）的影响；2）从不同角度研究免疫抑制是否参与对视网膜的保护。.本研究对于拓展FTY720作用机制的认识，研发视网膜光损伤的药物具有重要意义。

FTY720(fingolimod), an analogue to the sphingosine, is a unique immune suppressant characterized by sequestration of lymphocytes in secondary lymph nodes and inducing lymphopenia, and inhibition of T lymphocytes infiltration into the central nervous system. Conventionally, it is thought FTY720 is phosphorylated to form FTY720-phosphate (FTY720-P), and then FTY720-P binds to S1P receptors (S1PRs) and thereby shows its immune suppression effect. However, whether FTY720 is limited only as an immune suppressant is of debate. Recently it became evident that the action of FTY720 was more complex as it was found to directly target several other receptors or enzymes. Thus, FTY720 can bind to and inhibit the cannabinoid CB1 receptor, cytosolic phospholipase A2 (cPLA2), S1P lyase and ceramide synthase (CerS) activity. .The light induced retina degeneration (LIRD) model is a non-autoimmune animal model for retina degeneration. The basic pathological change in LIRD is photoreceptor apoptosis. It is clear that ceramide plays a key role in mediating apoptosis, and decreasing intracellular ceramide production can protect photoreceptor against apoptosis in Drosophila and retina degeneration model of RD10..In the LIRD model we found: 1.)the retinal ceramide increased significantly prior to photoreceptor apoptosis；2.)FTY720 could protect the retina against light damage；3.）However, the retinal protection from various dosages of FTY720 was discordant with the decreased extent of peripheral lymphocytes, which indicated the protection of FTY720 to retina might be independent of its immune suppression.So we hypothesized: 1.)in the LIRD model, the conventional immune suppression from FTY720 might not contribute to the retinal protection；2.）FTY720 might inhibit ceramide synthase activity and consequently decrease the ceramide production to protect photoreceptors against apoptosis..In this study, based on our initial results from LIRD model we are planning to detect FTY720's impact on key enzymes' gene/protein expression and activities in ceramide metabolism pathways, and changes of related metabolites to ceramide. Additionally, we'll detect the dosage and temporal effect of FTY720 on peripheral lymphocytes and retinal protection, and measure the local immune suppression effect of FTY720 on the light stressed retina..The study on retinal protective mechanism of FTY720, independent of immune suppression, might show its potent neuroprotective application to non-immune diseases, and be also valuable to develope the medicine for the prevention and treatment of the light-induced retinal damage.