Modulation of Membrane Trafficking of AQP5 in the Lens in Response to Changes in Zonular Tension Is Mediated by the Mechanosensitive Channel TRPV1

Abstract

In mice, the contraction of the ciliary muscle via the administration of pilocarpine reduces the zonular tension applied to the lens and activates the TRPV1-mediated arm of a dual feedback system that regulates the lens’ hydrostatic pressure gradient. In the rat lens, this pilocarpine-induced reduction in zonular tension also causes the water channel AQP5 to be removed from the membranes of fiber cells located in the anterior influx and equatorial efflux zones. Here, we determined whether this pilocarpine-induced membrane trafficking of AQP5 is also regulated by the activation of TRPV1. Using microelectrode-based methods to measure surface pressure, we found that pilocarpine also increased pressure in the rat lenses via the activation of TRPV1, while pilocarpine-induced removal of AQP5 from the membrane observed using immunolabelling was abolished by pre-incubation of the lenses with a TRPV1 inhibitor. In contrast, mimicking the actions of pilocarpine by blocking TRPV4 and then activating TRPV1 resulted in sustained increase in pressure and the removal of AQP5 from the anterior influx and equatorial efflux zones. These results show that the removal of AQP5 in response to a decrease in zonular tension is mediated by TRPV1 and suggest that regional changes to PH2O contribute to lens hydrostatic pressure gradient regulation.

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

“…Instead, nature chose to (bio)engineer a highly symmetric and interconnected growth shell system of lens fibers, supported by an unusual microcirculation that limits oxidative metabolism and conserves hydration, physiological homeostasis, and uniform nourishment in a cellular lens. In a biological lens, optical function is prolonged in the visual system over a lifetime ( 7 , 30 , 31 , 47 , 56 ). A relevant comparison can be made between hydration in a lens and the tardigrade, an extremotolerant organism known to be able to maintain its cellular structure under conditions of complete dehydration (anhydrobiosis) ( 150 ).…”

“…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 ).…”

“…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 ).…”