Fluid in Equals Fluid Out—Evidence for Circulating Fluid Fluxes in the Lens

Mathias et al. ¹ have proposed that the lens operates an internal microcirculation system that contributes to lens transparency by delivering nutrients to, and removing metabolic wastes from, internalized fiber cells while maintaining steady-state lens volume. In this model, Na⁺ and a convective flow of water are thought to enter the lens at its anterior and posterior poles via the extracellular space, and then exit the lens at the equator using an intercellular pathway mediated by gap junctions. The circulating flux of Na⁺ and its associated water flux are ultimately generated by the action of Na⁺ pumps expressed in surface lens cells that are concentrated at the equator.While the data on the existence of the circulating Na⁺ currents are firm, the existence of the fluid flows predicted by the model to follow Na⁺ have proven more difficult to directly measure. ^2,3 In the October issue, Candia et al. ⁴ utilized a novel 3-compartment Ussing chamber to provide the first actual measurements of fluid flow across the anterior, equator, and posterior surfaces of isolated bovine lenses. They show that under steady-state conditions, water uptake at the anterior and posterior poles of the lens is balanced by water loss at the equatorial surface a result which strongly suggests that fluid circulates through the lens. Furthermore, they show that the preincubation of lenses in either ouabain to inhibit Na⁺ pumps, or low sodium solutions to eliminate the circulating current, dramatically reduces fluid uptake at the poles and water loss at the equator, a result that links the fluid fluxes to the previously measured circulating Na⁺ currents. Having now validated a major component of the lens circulation system, the focus can now shift to the roles played by the system in maintaining the optical properties in the normal lens and how disruption of the system can lead to cataract—still the leading cause of blindness in the world today.