Ion pumps and cotransport systems in animal cell membranes maintain cellular ionic composition, transport electrolytes and fluid across epithelia and contribute towards the regulation of cell volume. Thus, it is reasonable to expect that ion pumps in the conjunctival epithelium should play a crucial role in maintaining an optimal tear film, a necessity for a normal functioning ocular surface. However, the transport properties of this epithelium, which interfaces with the tears, are virtually unknown. Therefore, this project will use electrophysiological, radio-labelled tracer and microspectrofluorometric techniques to characterize the transport functions of the rabbit conjunctiva. A thorough understanding of the basic physiology of this cell layer may be relevant to the design of future treatment modalities for dry eye syndrome - a disorder, affecting countless individuals worldwide, that can lead to the loss of vision. The PI will 1) determine the effects of biological activators (i.e., hormones, neurotransmitters, etc.) on macroscopic conductances across the rabbit conjunctival epithelium; 2) determine the nature of the Na+ absorptive process in the apical (tear-facing) surface of the epithelium; 3) complete the characterization of the C1- secreting mechanism; 4) determine the identity of electrically silent transporters that may be present, with emphasis on those usually associated with intracellular pH and cell volume regulation; and 5) determine the diffusional H20 permeability (Pdw) and osmotic permeability (Pf). From these studies the PI expects to be able to construct a model detailing whether this epithelium functions as a fluid secreting or absorbing epithelium. Based on this model, he will devise protocols to modify and possibly reverse the secretory/absorptive properties of the tissue.
