Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur-CONICET, Bahía Blanca, Buenos Aires, Argentina.
J Lipid Res. 2010 Jun;51(6):1247-62. doi: 10.1194/jlr.R003442. Epub 2010 Jan 25.
Many sphingolipids have key functions in the regulation of crucial cellular processes. Ceramide (Cer) and sphingosine (Sph) induce growth arrest and cell death in multiple situations of cellular stress. On the contrary, sphingosine-1-phosphate (S1P), the product of Sph phosphorylation, promotes proliferation, differentiation, and survival in different cell systems. This review summarizes the roles of these simple sphingolipids in different tissues and then analyzes their possible functions in the retina. Alterations in proliferation, neovascularization, differentiation, and cell death are critical in major retina diseases and collective evidence points to a role for sphingolipids in these processes. Cer induces inflammation and apoptosis in endothelial and retinal pigmented epithelium cells, leading to several retinopathies. S1P can prevent this death but also promotes cell proliferation that might lead to neovascularization and fibrosis. Recent data support Cer and Sph as crucial mediators in the induction of photoreceptor apoptosis in diverse models of oxidative damage and neurodegeneration, and suggest that regulating their metabolism can prevent this death. New evidence proposes a central role for S1P controlling photoreceptor survival and differentiation. Finally, this review discusses the ability of trophic factors to regulate sphingolipid metabolism and transactivate S1P signaling pathways to control survival and development in retina photoreceptors.
许多神经鞘脂具有调节关键细胞过程的关键功能。神经酰胺（Cer）和神经鞘氨醇（Sph）在多种细胞应激情况下诱导生长停滞和细胞死亡。相反，神经鞘氨醇-1-磷酸（S1P）是 Sph 磷酸化的产物，促进不同细胞系统的增殖、分化和存活。这篇综述总结了这些简单神经鞘脂在不同组织中的作用，然后分析了它们在视网膜中的可能功能。增殖、新生血管形成、分化和细胞死亡的改变在主要的视网膜疾病中至关重要，大量证据表明神经鞘脂在这些过程中起作用。Cer 在血管内皮细胞和视网膜色素上皮细胞中诱导炎症和细胞凋亡，导致多种视网膜病变。S1P 可以防止这种死亡，但也促进细胞增殖，可能导致新生血管形成和纤维化。最近的数据支持 Cer 和 Sph 作为多种氧化损伤和神经退行性变模型中诱导光感受器细胞凋亡的关键介质，并表明调节它们的代谢可以防止这种死亡。新的证据表明，S1P 控制光感受器存活和分化的中心作用。最后，这篇综述讨论了营养因子调节神经鞘脂代谢和转激活 S1P 信号通路以控制视网膜光感受器存活和发育的能力。
