Macura Irena Jovanovic, Djuricic Ivana, Major Tamara, Milanovic Desanka, Sobajic Sladjana, Kanazir Selma, Ivkovic Sanja
Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Front Nutr. 2024 Jan 24;10:1330414. doi: 10.3389/fnut.2023.1330414. eCollection 2023.
During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding.
The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation.
Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels.
Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.
在胎儿发育过程中，神经和视觉系统的正常发育依赖于母体通过胎盘转运补充ω-3脂肪酸。强烈建议孕妇通过增加ω-3的其他来源，如鱼油（FO）来改善饮食。这种补充与降低早产、先兆子痫和围产期抑郁症的风险有关。最近，已建议孕妇补充更高剂量的ω-3。鉴于ω-3脂肪酸，特别是二十二碳六烯酸（DHA），在维持视网膜和光感受器正常功能所需的微妙内环境平衡中起着关键作用，孕期和哺乳期高剂量补充鱼油（FO）对健康后代视网膜和视网膜色素上皮（RPE）的影响值得深入了解。
在高剂量补充FO后，评估视网膜和RPE中脂肪酸含量以及调节胆固醇稳态和DHA转运的基因表达变化。
我们的研究表明，尽管在孕期和哺乳期进行了高剂量FO治疗，但两个月大后代的视网膜和RPE中严格的DHA内环境平衡仍保持稳定。本研究的另一个重要发现是主要促进剂超家族结构域蛋白（Mfsd2a），一种主要的DHA转运体，其表达水平增加。Mfsd2a在发育过程中也是转胞吞作用的主要调节因子，Mfsd2a水平降低会对血管渗漏的发展构成重大风险。
血视网膜屏障（BRB）受损与多种眼部疾病的发生有关，更好地了解如何在发育过程中调控BRB中的转胞吞作用可以增强药物通过BRB的递送，或有助于中枢神经系统（CNS）屏障的修复。
