Endogenous bioelectric currents promote differentiation of the mammalian lens

The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lensequator are poorly understood. We detected that mature, denucleated lensfibers expressed high levels of the α1 and β1 subunits of Na+/K+-ATPase (ATP1A1 and ATP1B1of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem). In contrast, differentiating, nucleated lensfibre cells had little ATP1A1 and ATP1B1and a depolarized Vmem. Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lensepithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of β-crystallin, aquaporin-0 (AQP0) and the Beaded Filament Structural Protein 2 ( BFSP2) in lensepithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lensequator promotes differentiation of LECs into denucleated lensfibre cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lensdiseases and even promote regeneration of a complete new lensfollowing cataract surgery. This article is protected by copyright. All rights reserved