Regulation of water flow in the ocular lens: new roles for aquaporins

The ocular lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. The lens operates an internal microcirculation system that generates circulating fluxes of ions, water and nutrients that maintain the transparency and refractive properties of the lens. This flow of water generates a substantial hydrostatic pressure gradient which is regulated by a dual feedback system that uses the mechanosensitive channels TRPV1 and TRPV4 to sense decreases and increases, respectively, in the pressure gradient. This regulation of water flow (pressure) and hence overall lens water content, sets the two key parameters, lens geometry and the gradient of refractive index, which determine the refractive properties of the lens. Here we focus on the roles played by the aquaporin family of water channels in mediating lens water fluxes, with a specific focus on AQP5 as a regulated water channel in the lens. We show that in addition to regulating the activity of ion transporters, which generate local osmotic gradients that drive lens water flow, the TRPV1/4-mediated dual feedback system also modulates the membrane trafficking of AQP5 in the anterior influx pathway and equatorial efflux zone of the lens. Since both lens pressure and AQP5-mediated water permeability (PH2O${P_{{{\mathrm{H}}_{\mathrm{2}}}{\mathrm{O}}}}$) can be altered by changes in the tension applied to the lens surface via modulating ciliary muscle contraction we propose extrinsic modulation of lens water flow as a potential mechanism to alter the refractive properties of the lens to ensure light remains focused on the retina throughout life.image Abstract figure legend Lens water outflow through gap junctions generates a hydrostatic pressure (Pi) gradient that has been shown to regulate the optical properties of the lens. Contraction of the ciliary muscle causes a decrease in the zonular tension applied to the lens and an activation of the mechanosensitive channel TRPV1. Activation of TRPV1 increases lens hydrostatic pressure not only by modulating the activity of ion transporters but also by modulating water permeability (PH2O${P_{{{\mathrm{H}}_{\mathrm{2}}}{\mathrm{O}}}}$) by removing AQP5 from the membranes of fibre cells located in the equatorial efflux and in the anterior influx zones. Changes to the AQP5-meditated PH2O${P_{{{\mathrm{H}}_{\mathrm{2}}}{\mathrm{O}}}}$ contribute to an increase in intracellular osmolality, a decrease in water flow and an increase in the hydrostatic pressure gradient that regulates lens power.image

Automated summary

The ocular lens is an important determinant of overall vision quality. It operates an internal microcirculation system to maintain its transparency and refractive properties. Water flow generates a pressure gradient, regulated by a dual feedback system, that determines the lens geometry and refractive index gradient. Aquaporin water channels and TRPV1/4 channels play roles in mediating lens water fluxes and membrane trafficking, affecting lens water content and pressure. Extrinsic modulation of lens water flow may alter lens refractive properties.