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

Abstract

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.

• Authors: Sumin Gu, Sondip Biswas, Luis Rodriguez, Zhen Li, Yuting Li, Manuel A Riquelme, Wen Shi, Ke Wang, Thomas W White, Matthew Reilly, Woo-Kuen Lo, Jean X Jiang
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 60 Issue 12 Pg. 4021-4032 (09 03 2019) ISSN: 1552-5783 [Electronic] United States
• PMID: 31560767 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aquaporins
• Connexins
• Eye Proteins
• aquaporin 0
• connexin 50

Topics

• Animals
• Aquaporins (physiology)
• Cataract (metabolism, pathology)
• Cell Adhesion (physiology)
• Connexins (physiology)
• Eye Abnormalities (metabolism, pathology)
• Eye Proteins (physiology)
• Female
• Freeze Fracturing
• Lens, Crystalline (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Microscopy, Fluorescence
• Pupil (physiology)