Clusterin Seals The Ocular Surface Barrier In Mouse Dry Eye

Author

Aditi Bauskar
Wendy J. Mack
Jerome Mauris
Pablo Argüeso
Martin Heur
Barbara A. Nagel
Grant R. Kolar, Missouri University of Science and TechnologyFollow
Martin E. Gleave
Takahiro Nakamura
Shigeru Kinoshita
Janet Moradian-Oldak
Noorjahan Panjwani
Stephen C. Pflugfelder
Mark R. Wilson

Abstract

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.

Recommended Citation

A. Bauskar and W. J. Mack and J. Mauris and P. Argüeso and M. Heur and B. A. Nagel and G. R. Kolar and M. E. Gleave and T. Nakamura and S. Kinoshita and J. Moradian-Oldak and N. Panjwani and S. C. Pflugfelder and M. R. Wilson, "Clusterin Seals The Ocular Surface Barrier In Mouse Dry Eye," Plos One, vol. 10, no. 9, article no. e0138958, Public Library of Science, Sep 2015.

The definitive version is available at https://doi.org/10.1371/journal.pone.0138958

Department(s)

Biological Sciences

Publication Status

Open Access

Comments

National Eye Institute, Grant R01- DE013414

International Standard Serial Number (ISSN)

1932-6203

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2025 The Authors, All rights reserved.

Creative Commons Licensing

This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

24 Sep 2015

PubMed ID

26402857