Lens gap junctions in growth, differentiation, and homeostasis.

The cells of most mammalian organs are connected by groups of cell-to-cell channels called gap junctions. Gap junction channels are made from the connexin (Cx) family of proteins. There are at least 20 isoforms of connexins, and most tissues express more than 1 isoform. The lens is no exception, as it expresses three isoforms: Cx43, Cx46, and Cx50. A common role for all gap junctions, regardless of their Cx composition, is to provide a conduit for ion flow between cells, thus creating a syncytial tissue with regard to intracellular voltage and ion concentrations. Given this rather simple role of gap junctions, a persistent question has been: Why are there so many Cx isoforms and why do tissues express more than one isoform? Recent studies of lens Cx knockout (KO) and knock in (KI) lenses have begun to answer these questions. To understand these roles, one must first understand the physiological requirements of the lens. We therefore first review the development and structure of the lens, its numerous transport systems, how these systems are integrated to generate the lens circulation, the roles of the circulation in lens homeostasis, and finally the roles of lens connexins in growth, development, and the lens circulation.