Regulation of lens water content: Effects on the physiological optics of the lens.

The lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. Alterations to the refractive properties of the lens contribute to the process of emmetropisation in early childhood, and then the gradual loss in lens power that occurs throughout adulthood. In parallel to these changes to lens refractive power, age-dependent increases in lens stiffness and light scattering result in presbyopia and cataract, respectively. In recent years it has been confirmed that the lens operates an internal microcirculation system that generates circulating fluxes of ions, water and nutrients that maintain the refractive properties and transparency of the lens. By actively regulating lens water content, the microcirculation system controls two key parameters, lens geometry and the gradient of refractive index, which together determine the refractive properties of the lens. Furthermore, by delivering nutrients and antioxidants to the lens nucleus, the microcirculation system maintains lens transparency by preventing crystallin aggregation. Interestingly, the solubility, intramolecular packing and refractive index increment of crystallin proteins can be modulated by the ability of crystallin proteins to dynamically bind water, a processed called syneresis. In a series of previous studies it has been shown that the application of external pressure to the lens can induce syneresis. Since it is now known that lens water transport generates a substantial internal hydrostatic pressure gradient, we speculate that the microcirculation is capable of regulating crystallin function by altering the amount of water bound to lens proteins in the nucleus, where the pressure gradient and protein concentrations are the highest. Here we present evidence for the links between lens transport, pressure, syneresis and protein function. Furthermore, because the lens pressure gradient can be regulated by intrinsic and extrinsic stimuli, we suggest mechanisms via which this integrative system can be used to effect the changes to the refractive and transparent properties of the lens that are observed across our lifetime.