To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress – all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.

中文翻译：

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眼前：RPE 在衰老和疾病中的代谢景观


为了满足光感受器巨大的生物能量需求，葡萄糖和其他营养物质必须穿过视网膜色素上皮 （RPE），RPE 是位于视网膜外层和脉络膜（眼睛的主要血管层）之间界面的极化单层细胞。最近的研究揭示了视网膜外层的代谢生态系统，其中光感受器和 RPE 参与糖、氨基酸和其他代谢物的复杂交换。这种微妙的代谢平衡的扰动已在老化的视网膜以及年龄相关性黄斑变性 （AMD） 中被发现，AMD是西方世界失明的主要原因。在衰老和患病的视网膜中也很常见的是细胞因子水平升高、氧化应激、晚期糖基化终产物、生长因子信号增加和生物力学应激——所有这些都与非视网膜细胞类型和组织中的代谢失调有关。在此，我们概述了这些因素在视网膜稳态、衰老和疾病中的作用。我们讨论了它们对视网膜外组织和细胞类型中葡萄糖、线粒体、脂质和氨基酸代谢的影响，强调了它们诱导这些变化的信号通路。最后，我们讨论了未来研究的有希望的途径，调查这些病理状况对视网膜代谢的作用，可能提供新的治疗方法来对抗与年龄相关的视网膜疾病。