Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy
Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy
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Mfsd2a 过度表达可减轻糖尿病视网膜病变的血管功能障碍
DOI：
10.1016/j.phrs.2021.105755
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发表时间：
2021
影响因子：
9.3
通讯作者：
Ya-nan Li
中科院分区：
文献类型：
--
作者：
Chun-lin Zhang;Hai-ling Wang;Peng-cheng Li;Can-dong Hong;An-qi Chen;Yan-mei Qiu;Ai-ping Zeng;Yi-fan Zhou;Bo Hu;Ya-nan Li
糖尿病视网膜病变(DR)是糖尿病患者常见的并发症之一。目前，血管内皮细胞生长因子途径受到了广泛的研究。然而，约27%的患者视力预后较差，其中50%的患者在用雷尼比珠单抗治疗糖尿病黄斑水肿(DME)两年后仍有水肿。二十二碳六烯酸是主要的ω-3长链多不饱和脂肪酸(LC-PUFA)，可减少异常新生血管，减轻新生血管眼病。一项研究报告称，鱼油可将早产儿视网膜病变(ROP)的发生率降低约27.5%。尽管ω-3 LC-PUFAs对病理性视网膜新生血管有保护作用，但其治疗效果较低。调查为什么DHA治疗在一些患者中失败是很有趣的。在人的玻璃体液样品中，我们发现DR患者的玻璃体中DHA及其代谢产物占总脂肪酸的比例高于黄斑裂孔患者，而糖尿病患者的玻璃体液中DHA及DHA代谢产物的比例低于黄斑裂孔患者。氧诱导视网膜病变(OIR)模型和链脲佐菌素(STZ)模型中LPC-DHA转运体Mfsd2a的表达减少。在体外，Mfsd2a过表达抑制内皮细胞的增殖、迁移和囊泡跨细胞。此外，Mfsd2a过表达联合DHA饮食明显减少异常视网膜新生血管和血管渗漏，比单独使用Mfsd2a更有效。这些结果提示，部分DR患者DHA治疗失败与Mfsd2a低表达有关，Mfsd2a高表达联合DHA治疗可能是一种有效的治疗方法。
Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years’ treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.