TY - JOUR
T1 - Lipidomic analysis revealed n-3 polyunsaturated fatty acids suppressed choroidal thinning and myopia progression in mice
AU - Mori, Kiwako
AU - Kuroha, Sayoko
AU - Hou, Jing
AU - Jeong, Heonuk
AU - Ogawa, Mamoru
AU - Ikeda, Shin ichi
AU - Kang, Jing X.
AU - Negishi, Kazuno
AU - Torii, Hidemasa
AU - Arita, Makoto
AU - Kurihara, Toshihide
AU - Tsubota, Kazuo
N1 - Funding Information:
The authors thank X. Jiang, A. Shinojima, E. Yotsukura, Y. Zang, M. Ibuki, C. Shoda, Y. Miwa, H. Kunimi, and Y. Katada in the Laboratory of Photobiology, Keio University School of Medicine, A. Hori and M. Honda in the Laboratory for Metabolomics, RIKEN IMS, and H. Kawano from Mochida Pharmaceutical Co., Ltd. for their technical and administrative support. This work was supported by Grants‐in‐Aid for Scientific Research (KAKENHI, Grants 20K22743, 21K16882 K.M.), and 21H03096 (K.T.) from the Ministry of Education, Culture, Sports, Science and Technology. This work was also supported by a grant for myopia research from Tsubota Laboratory, Inc., Tokyo, Japan.
Funding Information:
The authors thank X. Jiang, A. Shinojima, E. Yotsukura, Y. Zang, M. Ibuki, C. Shoda, Y. Miwa, H. Kunimi, and Y. Katada in the Laboratory of Photobiology, Keio University School of Medicine, A. Hori and M. Honda in the Laboratory for Metabolomics, RIKEN IMS, and H. Kawano from Mochida Pharmaceutical Co., Ltd. for their technical and administrative support. This work was supported by Grants-in-Aid for Scientific Research (KAKENHI, Grants 20K22743, 21K16882 K.M.), and 21H03096 (K.T.) from the Ministry of Education, Culture, Sports, Science and Technology. This work was also supported by a grant for myopia research from Tsubota Laboratory, Inc., Tokyo, Japan.
Publisher Copyright:
© 2022 Federation of American Societies for Experimental Biology.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - choroidal thickness
KW - eicosapentaenoic acid
KW - lipidomic analysis
KW - myopia
KW - n-3 polyunsaturated fatty acid
UR - http://www.scopus.com/inward/record.url?scp=85129458508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129458508&partnerID=8YFLogxK
U2 - 10.1096/fj.202101947R
DO - 10.1096/fj.202101947R
M3 - Article
C2 - 35532744
AN - SCOPUS:85129458508
SN - 0892-6638
VL - 36
JO - FASEB Journal
JF - FASEB Journal
IS - 6
M1 - e22312
ER -