Connexin in Lens Physiology and Cataract Formation

Abstract

Connexins are a family of proteins that forms hemichannels that communicate the cytoplasm with the extracellular space. When two hemichannels [each one from two neighboring cells] make contact, they form a gap junction channel, which communicates the cytoplasm of adjacent cells. The molecular mechanisms that control the opening and closing of both functional hemichannels and gap junction channels is still matter of intense scrutiny. The lens is a transparent structure located in the anterior segment of the eye, which is critical for normal vision. Its main function is to refract the light, focusing it on the retina. Given this function, the lens requires great transparency and homogeneity which are attained by being avascular to avoid light scattering. To compensate for the lack of blood vessels, lens cells have intercellular connections formed by gap junction channels, which allow passive flux of nutrients and metabolites throughout the entire lens. Cataracts are produced by opacity of the lens, so less light reaches the retina. Recent evidence suggests that dysfunction of gap junction channels and hemichannels may induce cataract formation. Here we review general properties of gap junction channels and hemichannels. Then, we show the role of these channels in lens physiology and cataract formation with emphasis on rodent models lacking particular connexin genes and single point mutations in humans associated to hemichannel dysfunction. Finally, we raise the question of how environmental factors may affect hemichannel and gap junction activity and in turn induce or accelerate cataract formation by discussing the evidence that link molecular modifications [i.e phosphorylation and oxidation] of gap junction channels and hemichannels with cataract formation.