Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, 2020 Gravier Street, New Orleans, LA, 70112, USA.
Biostatistics, School of Public Health, Louisiana State University Health New Orleans, 2020 Gravier Street, New Orleans, LA, 70112, USA.
Exp Eye Res. 2023 Oct;235:109639. doi: 10.1016/j.exer.2023.109639. Epub 2023 Sep 1.
Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, we compared omega-3 (n-3) fatty acid with DHA (22:6) and omega-6 (n-6) fatty acid with arachidonic acid (AA; 20:4) pathways. n-3 PC(22:6/22:6, 44:12) and n-6 PC(20:4/20:4, 40:8) showed differences among male/female, macula/periphery, and normal/AMD retinas. Periphery of AMD retina males increased 44:12 abundance, while normal females increased 40:8 (all macula had an upward 40:8 tendency). We also showed that female AMD switched from n-3 to n-6 fatty acids; most changes in AMD occurred in the periphery of female AMD retinas. DHA and VLC-PUFA release from PCs leads to conversion in pro-survival NPD1 and ELVs. The loss of the neuroprotective precursors of ELVs in the retina periphery from AMD facilitates uncompensated stress and cell loss. In AMD, the female retina loses peripheral rods VLC-PUFAs to about 33% less than in males limiting ELV formation and its protective bioactivity.
二十二碳六烯酸（DHA；22:6）在视觉中起着关键作用，是超长链多不饱和脂肪酸（VLC-PUFA）的前体。二十二碳六烯酸（DHA）和磷脂酰胆碱（PC）sn-1 和 sn-2 位的 32 碳和 34 碳 VLC-PUFA 的释放导致细胞存活介质的合成，分别为 elovanoids（ELVs）和神经保护素 D1（NPD1）。通过基于 LC-MS/MS 的脂质组学分析和 MALDI 分子成像，评估来自年龄相关性黄斑变性（AMD）供体视网膜的黄斑和周边区域 DHA 相关脂质的可用性。我们发现，视网膜 DHA 和 VLC-PUFA 途径的减少导致合成 omega-3 ELVs 的前体减少，这可能导致盘状结构和光感受器丢失。此外，我们比较了 omega-3（n-3）脂肪酸与 DHA（22:6）和 omega-6（n-6）脂肪酸与花生四烯酸（AA；20:4）的途径。n-3 PC（22:6/22:6，44:12）和 n-6 PC（20:4/20:4，40:8）在男性/女性、黄斑/周边、正常/AMD 视网膜之间存在差异。AMD 男性视网膜周边区域 44:12 丰度增加，而正常女性 40:8 丰度增加（所有黄斑均有 40:8 向上趋势）。我们还表明，AMD 女性从 n-3 脂肪酸转变为 n-6 脂肪酸；AMD 中大多数变化发生在女性 AMD 视网膜的周边区域。PC 中 DHA 和 VLC-PUFA 的释放导致具有促生存作用的 NPD1 和 ELVs 的转化。AMD 患者视网膜周边区域 ELVs 的神经保护前体的丢失导致代偿性应激和细胞丢失。在 AMD 中，女性视网膜的周边杆状 VLC-PUFA 损失约为男性的 33%，从而限制了 ELV 的形成及其保护生物活性。
