Aqueous humor formation is mainly a composite of active secretion by the double layered ciliary process epithelium (inner nonpigmented and outer pigmented epithelium) and of ultrafiltration (dialysis in the presence of hydrostatic pressure). Final aqueous humor composition is determined by both of these actions which are influenced a number of factors including systemic and local metabolic alterations, humoral influences, circulatory changes and neurological modifications.
The aim of this proposal is to investigate transport processes in the isolate iris-ciliary body (I-CB) independent of these factors. Experimental techniques will include the following 1) Transepithelial measurement in the I-CB preparation of tissue potential difference, short-circuit current, tissue resistance, ionic fluxes and fluid transport to provide an overview of active transport processes in the ciliary epithelium. 2) Conventional ionic specific and pH microelectrode studies to characterize the steps in ion translocation across the double epithelial layer of the ciliary processes. 3) Patch-clamp studies on the inner cell membrane of the nonpigmented layer. In virto transepithelial, intracellular microelectrode, and patch-clamp micropipette measurements can provide insights into the normal physiology and active transport of the ciliary epithelium. Pharmacological studies will provide information on basic and altered states of ciliary epithelial secretory and transport processes. Agents to be investigated include adrenergic agonists and antagonists, carbonic anhydrase inhibitors, calcium channel blocking agents, and neuropeptides (e.g. anti-diuretic hormone, vasoactive intestinal polypeptide, etc). Knowledge of the mechanisms involved in the active production of aqueous humor, as well as the effects of pharmacological agents on active transport by the ciliary epithelium, will provide insights into glaucoma therapeutic modalities directed to reducing the rate of aqueous humor formation.
