Similar fundamental physiological processes can be marshalled by different cell types to achieve quite different goals. The overall objectives are to delineate those ion transport processes involved in aqueous humor formation across the ciliary epithelium, and those in corneal thickness regulation by the endothelium. To achieve these objectives we propose the following aims:
Aim I) To determine the relative contribution of transcellular and paracellular pathways to the overall conductance, and physiological and pharmacological behavior, of the isolated ciliary epithelium of the pigmented rabbit.
Aim II) To determine the relative contribution of transcellular and paracellular pathways to the overall conductance and physiology of the freshly dissected rabbit or tissue cultured rabbit or bovine corneal endothelium. To achieve these aims we will a) discriminate between transcellular and paracellular pathways by the use of specific agents such as ion pump inhibitors, ionophores and channel blockers, b) determine the intracellular concentration of ions such as Na+, H, Cl and K+ using fluroprobes and video-imaging techniques in the ciliary epithelium and corneal endothelium. We will evaluate the following hypotheses: 1) that HCO3 is important in ciliary epithelial ion transport processes; 2) that he non-pigmented epithelium is the major contributing layer to the physiological and pharmacological behaviour of ciliary epithelium; 3) that the paracellular pathway is of major importance in governing the ciliary epithelial physiology; 4) that entry of Na+ into corneal endothelial cells across the basolateral border is HCO3/CO2-dependent; 5) that Na+ leaves endothelial cells across the apical border by at least one other mechanism other than a Na+/HCO3- symport; and 6) that HCO3 - and Na+ can exit from the endothelial cell across the apical cell border through independent pathways. The data, collectively, will allow assessment of the importance of each cell layer and the paracellular pathway to the overall behaviour of the ciliary epithelium, and delineate the transport systems involve din aqueous humor formation. The pharmacological studies will provide data pertinent to aqueous humor formation. The pharmacological studies transport processes of the corneal endothelium will also be accurately delineated and the effects of pharmacological intervention assessed as a step towards being able to reduce clinical corneal edema.
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