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Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye
Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory di...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581869/ https://www.ncbi.nlm.nih.gov/pubmed/26402857 http://dx.doi.org/10.1371/journal.pone.0138958 |
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author | Bauskar, Aditi Mack, Wendy J. Mauris, Jerome Argüeso, Pablo Heur, Martin Nagel, Barbara A. Kolar, Grant R. Gleave, Martin E. Nakamura, Takahiro Kinoshita, Shigeru Moradian-Oldak, Janet Panjwani, Noorjahan Pflugfelder, Stephen C. Wilson, Mark R. Fini, M. Elizabeth Jeong, Shinwu |
author_facet | Bauskar, Aditi Mack, Wendy J. Mauris, Jerome Argüeso, Pablo Heur, Martin Nagel, Barbara A. Kolar, Grant R. Gleave, Martin E. Nakamura, Takahiro Kinoshita, Shigeru Moradian-Oldak, Janet Panjwani, Noorjahan Pflugfelder, Stephen C. Wilson, Mark R. Fini, M. Elizabeth Jeong, Shinwu |
author_sort | Bauskar, Aditi |
collection | PubMed |
description | Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye. |
format | Online Article Text |
id | pubmed-4581869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45818692015-10-01 Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye Bauskar, Aditi Mack, Wendy J. Mauris, Jerome Argüeso, Pablo Heur, Martin Nagel, Barbara A. Kolar, Grant R. Gleave, Martin E. Nakamura, Takahiro Kinoshita, Shigeru Moradian-Oldak, Janet Panjwani, Noorjahan Pflugfelder, Stephen C. Wilson, Mark R. Fini, M. Elizabeth Jeong, Shinwu PLoS One Research Article Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye. Public Library of Science 2015-09-24 /pmc/articles/PMC4581869/ /pubmed/26402857 http://dx.doi.org/10.1371/journal.pone.0138958 Text en © 2015 Bauskar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bauskar, Aditi Mack, Wendy J. Mauris, Jerome Argüeso, Pablo Heur, Martin Nagel, Barbara A. Kolar, Grant R. Gleave, Martin E. Nakamura, Takahiro Kinoshita, Shigeru Moradian-Oldak, Janet Panjwani, Noorjahan Pflugfelder, Stephen C. Wilson, Mark R. Fini, M. Elizabeth Jeong, Shinwu Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title | Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title_full | Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title_fullStr | Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title_full_unstemmed | Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title_short | Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye |
title_sort | clusterin seals the ocular surface barrier in mouse dry eye |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581869/ https://www.ncbi.nlm.nih.gov/pubmed/26402857 http://dx.doi.org/10.1371/journal.pone.0138958 |
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