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Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers

PURPOSE: Connexins and aquaporins play essential roles in maintaining lens homeostasis and transparency and there is a close physical and functional relationship between these two proteins. Aquaporin 0 (AQP0), in addition to its role in water transport in the lens, acts as a cell–cell adhesion molec...

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Autores principales: Gu, Sumin, Biswas, Sondip, Rodriguez, Luis, Li, Zhen, Li, Yuting, Riquelme, Manuel A., Shi, Wen, Wang, Ke, White, Thomas W., Reilly, Matthew, Lo, Woo-Kuen, Jiang, Jean X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779290/
https://www.ncbi.nlm.nih.gov/pubmed/31560767
http://dx.doi.org/10.1167/iovs.18-26270
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author Gu, Sumin
Biswas, Sondip
Rodriguez, Luis
Li, Zhen
Li, Yuting
Riquelme, Manuel A.
Shi, Wen
Wang, Ke
White, Thomas W.
Reilly, Matthew
Lo, Woo-Kuen
Jiang, Jean X.
author_facet Gu, Sumin
Biswas, Sondip
Rodriguez, Luis
Li, Zhen
Li, Yuting
Riquelme, Manuel A.
Shi, Wen
Wang, Ke
White, Thomas W.
Reilly, Matthew
Lo, Woo-Kuen
Jiang, Jean X.
author_sort Gu, Sumin
collection PubMed
description PURPOSE: Connexins and aquaporins play essential roles in maintaining lens homeostasis and transparency and there is a close physical and functional relationship between these two proteins. Aquaporin 0 (AQP0), in addition to its role in water transport in the lens, acts as a cell–cell adhesion molecule. Recently, we showed a new role of connexin (Cx) 50 in mediating cell–cell adhesion. However, the cooperative roles of these two proteins in the lens in vivo have not been reported. METHODS: We generated an AQP0/Cx50 double knockout (dKO) mouse model. Light, fluorescence, transmission thin section, and freeze-fracture electron microscopy, as well as wheat germ agglutinin and phalloidin labeling were used to evaluate lens structure. Mechanical properties of lenses were determined by mechanical compression testing. RESULTS: DKO mice exhibited small eyes and lenses with severe cataracts, along with lens posterior defects, including posterior capsule rupture. The dKO mouse lenses had severe structural disruption associated with increased spaces between lens fiber cells when compared with wild-type lenses or lenses deficient in either Cx50 or AQP0. DKO mice also exhibited greater reduction in lens size compared with Cx50 KO mice. Gap-junction plaque size was greatly decreased in cortical fiber cells in dKO mice. Moreover, lens stiffness and elasticity were completely diminished, exhibiting a gelatinous texture in adult dKO mice. CONCLUSIONS: This novel mouse model reveals that Cx50 and AQP0 play an important role in mediating cell–cell adhesion function in the lens fiber cells and their deficiency impairs lens fiber organization, integrity, mechanical properties, and lens development.
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spelling pubmed-67792902019-10-09 Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers Gu, Sumin Biswas, Sondip Rodriguez, Luis Li, Zhen Li, Yuting Riquelme, Manuel A. Shi, Wen Wang, Ke White, Thomas W. Reilly, Matthew Lo, Woo-Kuen Jiang, Jean X. Invest Ophthalmol Vis Sci Lens PURPOSE: Connexins and aquaporins play essential roles in maintaining lens homeostasis and transparency and there is a close physical and functional relationship between these two proteins. Aquaporin 0 (AQP0), in addition to its role in water transport in the lens, acts as a cell–cell adhesion molecule. Recently, we showed a new role of connexin (Cx) 50 in mediating cell–cell adhesion. However, the cooperative roles of these two proteins in the lens in vivo have not been reported. METHODS: We generated an AQP0/Cx50 double knockout (dKO) mouse model. Light, fluorescence, transmission thin section, and freeze-fracture electron microscopy, as well as wheat germ agglutinin and phalloidin labeling were used to evaluate lens structure. Mechanical properties of lenses were determined by mechanical compression testing. RESULTS: DKO mice exhibited small eyes and lenses with severe cataracts, along with lens posterior defects, including posterior capsule rupture. The dKO mouse lenses had severe structural disruption associated with increased spaces between lens fiber cells when compared with wild-type lenses or lenses deficient in either Cx50 or AQP0. DKO mice also exhibited greater reduction in lens size compared with Cx50 KO mice. Gap-junction plaque size was greatly decreased in cortical fiber cells in dKO mice. Moreover, lens stiffness and elasticity were completely diminished, exhibiting a gelatinous texture in adult dKO mice. CONCLUSIONS: This novel mouse model reveals that Cx50 and AQP0 play an important role in mediating cell–cell adhesion function in the lens fiber cells and their deficiency impairs lens fiber organization, integrity, mechanical properties, and lens development. The Association for Research in Vision and Ophthalmology 2019-09 /pmc/articles/PMC6779290/ /pubmed/31560767 http://dx.doi.org/10.1167/iovs.18-26270 Text en Copyright 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Lens
Gu, Sumin
Biswas, Sondip
Rodriguez, Luis
Li, Zhen
Li, Yuting
Riquelme, Manuel A.
Shi, Wen
Wang, Ke
White, Thomas W.
Reilly, Matthew
Lo, Woo-Kuen
Jiang, Jean X.
Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title_full Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title_fullStr Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title_full_unstemmed Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title_short Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers
title_sort connexin 50 and aqp0 are essential in maintaining organization and integrity of lens fibers
topic Lens
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779290/
https://www.ncbi.nlm.nih.gov/pubmed/31560767
http://dx.doi.org/10.1167/iovs.18-26270
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