Abstract
Purpose :
The role of cell adhesion in lens transparency is difficult to assess because of the developmental and physiological roles known adhesion proteins play in this process. We have discovered that Arvcf, a member of the p120-catenin subfamily of catenins which binds to the juxtamembrane domain of cadherins and regulates GTPase signaling, is strongly expressed in lens fiber cells and is important for maintaining lens transparency with age. Arvcf knock-out (KO) mice develop cortical cataracts at approximately 6 months of age without other developmental anomalies. Because of its potential role in lens fiber cell adhesion, it is hypothesized that the loss of Arvcf promotes cortical opacities due to a reduction in the stability of the cadherin complex and adhesion junctions between lens fiber cells.
Methods :
The role for Arvcf in the lens was tested through biochemical screening and histological analysis of lenses from control and knock-out mice. Additionally, high-resolution microscopy methods including super-resolution confocal and scanning electron microscopy were utilized to assess changes to fiber cell morphology and protein localization.
Results :
Lens fiber cell lysates from control and Arvcf KO mice were analyzed via mass spectroscopy following immunoprecipitation with N-cadherin antibody in order to determine how protein interactions were affected by the loss of Arvcf. We found that several proteins with known roles in promoting the stability of adherens junctions to have a significantly reduced ability to associate with N-cadherin including b-catenin, a-N-catenin and actin. Confocal analysis and quantitative localization experiments confirmed a significant reduction of these proteins between the junctions of lens fiber cells. Super-resolution imaging also demonstrated that the localization of cadherin associated proteins is significantly attenuated within the normally Arvcf-rich interlocking protrusions that emanate from the tricellular junctions of lens fiber cells in the region of cortical transparency loss of the lens.
Conclusions :
These data indicate that the Arvcf protein maintains cortical transparency through the stabilization of the cadherin complex within interlocking protrusions and bicellular junctions of lens fiber cells. In addition, these results suggest that cortical cataracts may be caused by a decrease in cell adhesion between lens fiber cells.
This is a 2021 ARVO Annual Meeting abstract.