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A. I. Son, M. A. Cooper, D. Komlos, Y. Sun, N. J. Kleiman, R. Zhou; Loss of Ephrin-A5 Leads to Lens Fiber Cell Disorganization and Cataracts. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1224.
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© ARVO (1962-2015); The Authors (2016-present)
Interactions between lens fiber cells are highly regulated to form a functional, transparent crystalline lens. This communication between fiber cells is made possible through the use of extensive intercellular adhesion complexes including adherens and gap junctions. Nevertheless, signals controlling fiber cell communication remain poorly understood. To better understand the molecular mechanisms of fiber cell interaction, we examined roles of the Eph family tyrosine kinase ligand ephrin-A5 during lens development and the mechanisms by which the adherens junction complex is regulated.
Ephrin-A5 wild-type and null mice were examined at various ages to determine cataract progression utilizing slit-lamp biomicroscopy and Scheimpflug imaging. Sectioned lens tissue was examined by H&E staining. Protein expression and localization was determined via immunohistochemistry and western blot analysis.
87% of ephrin-A5-/- adult mice develop mature opacities with frequent lens capsule rupture. Heterozygous animals appear normal. Lens fiber cells from null mice appear rounded and irregular in cross-section. Loss of ephrin-A5 reduces the activation of the Eph receptor EphA2 and disrupts the localization of the adherens junction molecule N-cadherin. Ephrin-A5 and EphA2 appear to promote interaction between N-cadherin and beta-catenin.
These findings identify critical regulation of lens development, and possibly disease, by a new family of molecules, ephrin-A5 and its receptor EphA2. The ephrin-A5/EphA2 ligand-receptor pair appears to regulate the adherens junction complex through the enhancement of the interaction between N-cadherin and beta-catenin, thus maintaining proper lens fiber cell adhesion.
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