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Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease

Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-hydroxy fatty acids (OAHFAs), a subclass of these lipids, are thought to be involved in connecting the lipid and aqueous layers in tears, although...

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Autores principales: Miyamoto, Masatoshi, Sassa, Takayuki, Sawai, Megumi, Kihara, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138607/
https://www.ncbi.nlm.nih.gov/pubmed/32252890
http://dx.doi.org/10.7554/eLife.53582
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author Miyamoto, Masatoshi
Sassa, Takayuki
Sawai, Megumi
Kihara, Akio
author_facet Miyamoto, Masatoshi
Sassa, Takayuki
Sawai, Megumi
Kihara, Akio
author_sort Miyamoto, Masatoshi
collection PubMed
description Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-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 ω-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 1ω and 2ω) 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.
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spelling pubmed-71386072020-04-08 Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease Miyamoto, Masatoshi Sassa, Takayuki Sawai, Megumi Kihara, Akio eLife Biochemistry and Chemical Biology Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-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 ω-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 1ω and 2ω) 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. eLife Sciences Publications, Ltd 2020-04-07 /pmc/articles/PMC7138607/ /pubmed/32252890 http://dx.doi.org/10.7554/eLife.53582 Text en © 2020, Miyamoto et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Miyamoto, Masatoshi
Sassa, Takayuki
Sawai, Megumi
Kihara, Akio
Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title_full Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title_fullStr Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title_full_unstemmed Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title_short Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
title_sort lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138607/
https://www.ncbi.nlm.nih.gov/pubmed/32252890
http://dx.doi.org/10.7554/eLife.53582
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