Electrolyte and Fluid Transport in the Ocular Membranes

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

DESCRIPTION: At the macroscopic level, the ocular lens appears as a relatively simple structure with the sole role of focusing light upon the retina. However, contemporary studies have underscored the dynamic nature of the organ with a host of compartmentalized physiological processes necessary for transparency. Given this emphasis, as well as recent original findings of this laboratory, this application proposes to exclusively study electrolyte and fluid transport mechanisms of the lens. As such, the following hypotheses are advanced. 1) That a fluid circulation exists inside the avascular lens. This fluid enters and leaves the lens at different regions completing a loop around the lens surface. Further, this circulation is driven by ionic transport mechanisms that are also non-uniformly distributed around the lens surface. 2) That ubiquitously expressed epithelial transport mechanisms can be functionally distinguished based upon their location within either the polar or equatorial lens epithelium. 3) That a volume change due to fluid traversing the surface of the lens occurs during accommodation. The work proposed to addresses the first hypothesis is designed to empirically test an earlier hypothetical concept initially proposed by Mathias and Rae. The latter hypothesis is related to the general theme of this project, which proposes studies on the distribution of fluid flows across the lens surface. To examine the above hypotheses, electrophysiological, radiolabeled tracer and fluorometric techniques will be used in three specific aims on bovine and rabbit lens models: 1) to determine the magnitude and direction of net fluid movement across intact lenses and its relation to the spatial distribution of currents circulating around the lens surface; 2) to measure the functional activity of transport elements about the surface of the lens, given recent indications for regional heterogeneity; and 3) to demonstrate, using an isolated ciliary body-lens preparation as well as isolated lenses, a possible fluid flow that seems to occur during accommodation. From the accomplishment of these aims, data relevant to the understanding of the mechanisms underlying lens homeostasis will be obtained. Such information is important, because the mechanisms by which the lens maintains its clarity remain obscure, and cataract remains a major cause of blindness worldwide.