Connexins in lens development and cataractogenesis

The lens is an avascular organ that transmits and focuses light images onto the retina. Intercellular gap junction channels, formed by at least three different connexin protein subunits, alpha 1 (connexin43 or Gja1), alpha 3 (connexin46 or Gja3) and alpha 8 (connexin50 or Gja8), are utilized to transport metabolites, ions and water in the lens. In combination with physiological and biochemical analyses, recent genetic studies have significantly improved our understanding about the roles of diverse gap junction channels formed by alpha 3 and alpha 8 connexin subunits during lens development and cataract formation. These studies have demonstrated that alpha 3 connexin is essential for lens transparency while alpha 8 connexin is important for lens growth and transparency. Diverse gap junction channels formed by alpha 3 and alpha 8 subunits are important for the differentiation, elongation and maturation of lens fiber cells. Aberrant gap junction communication, caused by alterations of channel assembly, channel gating or channel conductance, can lead to different types of cataracts. These findings provide some molecular insights for essential roles of connexins and gap junctions in lens formation and the establishment and maintenance of lifelong lens transparency.