Laboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Laboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Pharmacol Ther. 2023 Jul;247:108440. doi: 10.1016/j.pharmthera.2023.108440. Epub 2023 May 16.
The fatty acid composition of photoreceptor outer segment (POS) phospholipids diverges from other membranes, being highly enriched in polyunsaturated fatty acids (PUFAs). The most abundant PUFA is docosahexaenoic acid (DHA, C22:6n-3), an omega-3 PUFA that amounts to over 50% of the POS phospholipid fatty acid side chains. Interestingly, DHA is the precursor of other bioactive lipids such as elongated PUFAs and oxygenated derivatives. In this review, we present the current view on metabolism, trafficking and function of DHA and very long chain polyunsaturated fatty acids (VLC-PUFAs) in the retina. New insights on pathological features generated from PUFA deficient mouse models with enzyme or transporter defects and corresponding patients are discussed. Not only the neural retina, but also abnormalities in the retinal pigment epithelium are considered. Furthermore, the potential involvement of PUFAs in more common retinal degeneration diseases such as diabetic retinopathy, retinitis pigmentosa and age-related macular degeneration are evaluated. Supplementation treatment strategies and their outcome are summarized.
光感受器外段（POS）磷脂的脂肪酸组成与其他膜不同，高度富含多不饱和脂肪酸（PUFAs）。最丰富的多不饱和脂肪酸是二十二碳六烯酸（DHA，C22:6n-3），一种ω-3 多不饱和脂肪酸，占 POS 磷脂脂肪酸侧链的 50%以上。有趣的是，DHA 是其他生物活性脂质的前体，如长链多不饱和脂肪酸和氧化衍生物。在这篇综述中，我们介绍了 DHA 和超长链多不饱和脂肪酸（VLC-PUFAs）在视网膜中的代谢、运输和功能的最新观点。讨论了酶或转运体缺陷的 PUFA 缺乏小鼠模型和相应患者产生的病理特征的新见解。不仅是神经视网膜，视网膜色素上皮的异常也被认为是相关的。此外，还评估了多不饱和脂肪酸在更常见的视网膜变性疾病（如糖尿病性视网膜病变、色素性视网膜炎和年龄相关性黄斑变性）中的潜在作用。总结了补充治疗策略及其结果。
