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

Abstract

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 () 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

The significance of growth shells in development of symmetry, transparency, and refraction of the human lens

“…The overlap is part of the 3-D interconnected suture planes, extending from the surface into the embryonic nucleus. The suture can act as a channel carrying fluid containing ions, nutrients, soluble factors, and antioxidants that regulate and maintain symmetric structure ( 7 , 22 , 41 , 42 ). When normal fiber differentiation is disrupted, the sutures appear abnormal ( 22 ).…”

“…Hydrostatic pressure as high as 335 mm Hg centrally, falls to 0 mm Hg at the periphery, creating a pressure gradient for driving flow. The activity and localization of channels in the fiber membranes regulate flow and are critical for the optics of the visual system ( 7 , 11 , 31 , 42 , 45 , 47 , 50 , 54 ).…”

“…In the absence of vasculature, a simple hypothesis is that these sinusoidal oscillations are the structural basis for uniform symmetric fluid flow, known as microcirculation. If St fibers are spatial organizing centers for symmetric SSh fiber elongation, then the microcirculation can facilitate uniform fluid flow into the growth shells, anteriorly and posteriorly, to carry nutrients, growth factors, and protective molecules deep into the lens to organize and maintain function ( Figure 2 ) ( 7 , 42 , 45 ). Recent studies report the importance of uniform, symmetric fluid flow in the control of hydration, ion homeostasis, refraction, and transparency in the biological lens ( 31 , 32 , 42 , 45 – 47 ).…”