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  2. Lipidomic analysis revealed n-3 polyunsaturated fatty acids suppressed choroidal thinning and myopia progression in mice

Lipidomic analysis revealed n-3 polyunsaturated fatty acids suppressed choroidal thinning and myopia progression in mice

  • FASEB J. 2022 Jun;36(6):e22312. doi: 10.1096/fj.202101947R.
Kiwako Mori 1 2 Sayoko Kuroha 2 3 4 Jing Hou 1 2 Heonuk Jeong 1 2 Mamoru Ogawa 1 3 Shin-Ichi Ikeda 1 2 Jing X Kang 5 Kazuno Negishi 1 Hidemasa Torii 1 2 Makoto Arita 3 4 6 Toshihide Kurihara 1 2 Kazuo Tsubota 1 7
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
  • 2 Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan.
  • 3 Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, Japan.
  • 4 Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 5 Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 6 Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • 7 Tsubota Laboratory, Inc., Tokyo, Japan.
Abstract

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.

Keywords

choroidal thickness; eicosapentaenoic acid; lipidomic analysis; myopia; n-3 polyunsaturated fatty acid.

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