Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan.
FASEB J. 2022 Jun;36(6):e22312. doi: 10.1096/fj.202101947R.
Myopia is increasing worldwide and its preventable measure should urgently be pursued. N-3 polyunsaturated fatty acids (PUFAs) have been reported to have various effects such as vasodilative and anti-inflammatory, which myopia may be involved in. This study is to investigate the inhibitory effect of PUFAs on myopia progression. A lens-induced myopia (LIM) model was prepared using C57B L6/J 3-week-old mice, which were equipped with a -30 diopter lens to the right eye. Chows containing two different ratios of n-3/n-6 PUFA were administered to the mice, and myopic shifts were confirmed in choroidal thickness, refraction, and axial length in the n-3 PUFA-enriched chow group after 5 weeks. To exclude the possibility that the other ingredients in the chow may have taken the suppressive effect, fat-1 transgenic mice, which can produce n-3 PUFAs endogenously, demonstrated significant suppression of myopia. To identify what elements in n-3 PUFAs took effects on myopia suppression, enucleated eyes were used for targeted lipidomic analysis, and eicosapentaenoic acid (EPA) were characteristically distributed. Administration of EPA to the LIM model confirmed the inhibitory effect on choroidal thinning and myopia progression. Subsequently, to identify the elements and the metabolites of fatty acids effective on myopia suppression, targeted lipidomic analysis was performed and it demonstrated that metabolites of EPA were involved in myopia suppression, whereas prostaglandin E2 and 14,15-dihydrotestosterone were associated with progression of myopia. In conclusion, EPA and its metabolites are related to myopia suppression and inhibition of choroidal thinning.
近视在全球范围内不断增加,应紧急采取预防措施。已报道 n-3 多不饱和脂肪酸 (PUFA) 具有多种作用,如血管扩张和抗炎作用,而近视可能与这些作用有关。本研究旨在探讨 PUFAs 对近视进展的抑制作用。使用 3 周龄 C57B L6/J 小鼠制备晶状体诱导性近视 (LIM) 模型,将 -30 屈光度透镜置于右眼。给小鼠喂食含有两种不同 n-3/n-6 PUFA 比例的膳食,在富含 n-3 PUFA 的膳食组中,5 周后确认脉络膜厚度、屈光度和眼轴的近视漂移。为排除膳食中的其他成分可能具有抑制作用的可能性,使用可以内源性产生 n-3 PUFAs 的 Fat-1 转基因小鼠进行了实验,结果表明近视得到了显著抑制。为了确定 n-3 PUFAs 中的哪些成分对近视抑制有作用,对去眼后眼进行靶向脂质组学分析,发现二十碳五烯酸 (EPA) 有特征性分布。向 LIM 模型中给予 EPA 证实了其对脉络膜变薄和近视进展的抑制作用。随后,为了确定对近视抑制有效的脂肪酸的元素和代谢物,进行了靶向脂质组学分析,结果表明 EPA 的代谢物参与了近视抑制,而前列腺素 E2 和 14,15-二氢睾酮与近视进展有关。总之,EPA 及其代谢物与近视抑制和脉络膜变薄抑制有关。