PDF(Pubmed)
Abstract：
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.
摘要：
二十二碳六烯酸(DHA;22:6)在视觉中起关键作用,并且是超长链多不饱和脂肪酸(VLC-PUFA)的前体。磷脂酰胆碱（PC）的sn-1和sn-2释放32-和34-碳VLC-PUFA和DHA导致细胞存活介质的合成，elovanoid(ELVs)和神经保护素D1(NPD1)，分别。通过基于LC-MS/MS的脂质组学分析和MALDI-分子成像评估年龄相关性黄斑变性(AMD)供体视网膜的黄斑和外周的DHA相关脂质的可用性。我们发现减少的视网膜DHA和VLC-PUFA途径从前体合成omega-3ELV，这可能导致改变的圆盘和光感受器损失。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)途径。n-3PC(22:6/22:6,44:12)和n-6PC(20:4/20:4,40:8)显示男性/女性之间的差异，黄斑/周边，和正常/AMD视网膜。AMD男性视网膜边缘增加44:12丰度，而正常女性增加40:8（所有黄斑都有40:8的趋势）。我们还显示，女性AMD从n-3脂肪酸转变为n-6脂肪酸；AMD的大多数变化发生在女性AMD视网膜的外围。从PC释放的DHA和VLC-PUFA导致前存活NPD1和ELV的转化。来自AMD的视网膜周边中ELV的神经保护性前体的损失促进了未补偿的应激和细胞损失。在AMD中，女性视网膜失去外周杆VLC-PUFAs，比男性减少约33％，限制了ELV的形成及其保护性生物活性。
