The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (VLC-PUFAs,n-3, ≥ 28 carbons) are at the sn-1 of this PC molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes. Here, we review the structures and stereochemistry of novel elovanoid (ELV)-N32 and ELV-N34 to be ELV-N32: (14Z,17Z,20R,21E,23E,25Z,27S,29Z)-20,27-dihydroxydo-triaconta-14,17,21,23,25,29-hexaenoic acid; ELV-N34: (16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxytetra-triaconta-16,19,23,25,27,31-hexaenoic acid. ELVs are low-abundance, high-potency, protective mediators. Their bioactivity includes enhancing of anti-apoptotic and pro-survival protein expression with concomitant downregulation of pro-apoptotic proteins when RPE is confronted with uncompensated oxidative stress (UOS). ELVs also target PRC/RPE senescence gene programming, the senescence secretory phenotype in the interphotoreceptor matrix (IPM), as well as inflammaging (chronic, sterile, low-grade inflammation). An important lesson on neuroprotection is highlighted by the ELV mediators that target the terminally differentiated PRC and RPE, sustaining a beautifully synchronized renewal process. The role of ELVs in PRC and RPE viability and function uncovers insights on disease mechanisms and the development of therapeutics for age-related macular degeneration (AMD), Alzheimer's disease (AD), and other pathologies.

中文翻译：

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概述 N32 和 N34 elovanoids 如何通过保护视网膜色素上皮细胞和感光器来维持视力。

必需脂肪酸 DHA（22:6、omega-3 或 n-3）富含中枢神经系统感光细胞 (PRC)、突触、线粒体等的膜生物发生和功能，并且是这些细胞膜生物发生和功能所必需的。PRC DHA 在磷脂酰胆碱 (PC) 的 sn-2 处变成酰基链，占 PRC 外段磷脂的 50% 以上，在此发生光转导。极长链 PUFA（VLC-PUFA，n-3，≥ 28 个碳）位于该 PC 分子种类的 sn-1 处，并与视紫红质相互作用。PRC 每天脱落其尖端（富含 DHA 的膜盘），这些膜盘反过来被视网膜色素上皮 (RPE) 吞噬，其中 DHA 被回收回 PRC 内部节段，用于新感光膜的生物发生。在这里，我们回顾了新型 elovanoid (ELV)-N32 和 ELV-N34 的结构和立体化学，即 ELV-N32: (14Z,17Z,20R,21E,23E, 25Z,27S,29Z)-20,27-二羟基三十烷-14,17,21,23,25,29-己烯酸；ELV-N34：(16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-二羟基四-三十-16,19,23,25,27,31-己酸。ELV 是低丰度、高效力的保护性介质。它们的生物活性包括当 RPE 面临无代偿性氧化应激 (UOS) 时，增强抗凋亡和促存活蛋白表达，同时下调促凋亡蛋白。ELV 还针对 PRC/RPE 衰老基因编程、光感受器间基质 (IPM) 中的衰老分泌表型以及炎症（慢性、无菌、低度炎症）。ELV 介体强调了神经保护的一个重要教训，它针对终末分化的 PRC 和 RPE，维持完美同步的更新过程。