Figure 9.

Diagram of the mechanism of connexin hemichannels activated by FFSS and the mechanism of glucose and GSH transport to achieve lens fiber homeostasis. (A) FFSS induced by flow of fluid in the microcirculation leads to conformational activation of integrin α6β1. Activated integrin α6β1 enhances the association with C-terminus of Cx50 (black tail) and facilitates connexin hemichannels opening and the transport of GLU and GSH into lens fiber cells. (B) Cx50 hemichannels act as a transport portal for the uptake of GLU and GSH into the outer cortical fibers when glucose and GSH concentrations in the extracellular space are higher than those of the intracellular space (1). Cx50 hemichannels could also release GSH by outer lens epithelium/immature fibers when GSH concentration is higher intracellularly than extracellularly (2). This process helps GSH diffuse to proximal lens fiber cells. Glucose might not be able to release from fiber cells because glucose turns to glucose-6-phosphate rapidly inside cells (Kinoshita, 1965). Because of the physiological barrier (Michael and Bron, 2011), nutrients and antioxidants taking up from outer cortical fibers will be transported from outer lens to the nuclear fibers through gap junctions, likely by Cx46 (Slavi et al., 2014). In the nuclear fibers, because of the absence of integrin α6β1 and truncation of Cx50 at its C-terminus, hemichannels formed by truncated Cx50 (green) are not responsive to mechanical stimulation and thus remain closed. In this diagram: HC, hemichannel; yellow, full-length HC; green, truncated HC; GJ, gap junction; GLU (red hexagon), glucose; red hexagon with green dots, glucose-6-phosphate.