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(O-Acyl)-\u03c9-hydroxy fatty acids (OAHFAs), a subclass of these lipids, are thought to be involved in connecting the lipid and aqueous layers in tears, although their actual function and synthesis pathway have to date remained unclear. Here, we reveal that the fatty acid \u03c9-hydroxylase Cyp4f39 is involved in OAHFA production. Cyp4f39-deficient mice exhibited damaged corneal epithelium and shortening of tear film break-up time, both indicative of dry eye disease. In addition, tears accumulated on the lower eyelid side, indicating increased tear surface tension. In Cyp4f39-deficient mice, the production of wax diesters (type 1\u03c9 and 2\u03c9) and cholesteryl OAHFAs was also impaired. These OAHFA derivatives show intermediate polarity among meibum lipids, suggesting that OAHFAs and their derivatives contribute to lipid polarity gradient formation for tear film stabilization.<\/jats:p>","DOI":"10.7554\/elife.53582","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T20:00:45Z","timestamp":1586203245000},"source":"Crossref","is-referenced-by-count":55,"title":["Lipid polarity gradient formed by \u03c9-hydroxy lipids in tear film prevents dry eye disease"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-7438","authenticated-orcid":true,"given":"Masatoshi","family":"Miyamoto","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-9829","authenticated-orcid":true,"given":"Takayuki","family":"Sassa","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-802X","authenticated-orcid":true,"given":"Megumi","family":"Sawai","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5889-0788","authenticated-orcid":true,"given":"Akio","family":"Kihara","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0053","article-title":"Involucrin expression in the corneal epithelium: an essential role for Sp1 transcription factors","volume":"46","author":"Adhikary","year":"2005","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"12843","DOI":"10.1073\/pnas.0802607105","article-title":"Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids","volume":"105","author":"Agbaga","year":"2008","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S1542-0124(12)70150-7","article-title":"The contribution of meibomian disease to dry eye","volume":"2","author":"Bron","year":"2004","journal-title":"The Ocular Surface"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1001\/archopht.1969.00990020543020","article-title":"Hydrodynamics of blinking. 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