Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

中文翻译：

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鞘脂在视网膜生理学和病理学中发挥着关键作用。

鞘脂已成为参与许多生理和病理过程调节的生物活性脂质。在视网膜中，它们已被确定参与许多过程，例如神经元存活和死亡、神经元和血管细胞的增殖和迁移、炎症和新血管形成。因此，鞘脂失调对于视网膜疾病的发生和进展至关重要。本综述探讨了鞘脂与视网膜生理学和疾病的关系。在青光眼、年龄相关性黄斑变性 (AMD) 和色素性视网膜炎等视网膜病变动物模型中，神经酰胺 (Cer) 是神经元和视网膜色素上皮细胞炎症和死亡的常见介质。1-磷酸鞘氨醇 (S1P) 具有相反的作用，预防感光细胞和神经节细胞变性，同时促进 AMD、青光眼和促纤维化疾病中的炎症、纤维化和新生血管形成。Cer、S1P 和 1-磷酸神经酰胺的改变也可能导致葡萄膜炎。值得注意的是，使用防止 Cer 增加或调节 S1P 信号传导的抑制剂，例如多球菌素、地昔帕明和芬戈莫德 (FTY720)，可以保留神经元活力和视网膜功能。这些发现强调了鞘脂代谢网络的改变与多种视网膜病变的病因学的相关性，并强调了调节其代谢对于设计新的治疗方法的潜力。1-磷酸神经酰胺也可能导致葡萄膜炎。值得注意的是，使用防止 Cer 增加或调节 S1P 信号传导的抑制剂，例如多球菌素、地昔帕明和芬戈莫德 (FTY720)，可以保留神经元活力和视网膜功能。这些发现强调了鞘脂代谢网络的改变与多种视网膜病变的病因学的相关性，并强调了调节其代谢对于设计新的治疗方法的潜力。1-磷酸神经酰胺也可能导致葡萄膜炎。值得注意的是，使用防止 Cer 增加或调节 S1P 信号传导的抑制剂，例如多球菌素、地昔帕明和芬戈莫德 (FTY720)，可以保留神经元活力和视网膜功能。这些发现强调了鞘脂代谢网络的改变与多种视网膜病变的病因学的相关性，并强调了调节其代谢对于设计新的治疗方法的潜力。