PEPTIDE AND PROBE MODULATION OF AQUEOUS DYNAMICS

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The objectives of this proposal are the correlation of 1) the in vitro localization by histochemical and immunohistochemical methods of various neuropeptides in the anterior segment of the eye and 2) the in vitro effects of various selective molecular probes on ionic cellular events in the ciliary epithelium with the in vivo physiological and pharmacological effects of these agents on intraocular pressure. Investigations will provide information on the role of neuropeptides (low molecular weight, bioactive endogenous proteins) and molecular probes (chemical inhibitors of cellular ionic transport, exchange, or channels) as physiologic regulators or pharmacologic modulators of aqueous humor dynamics. Results will provide insights into factors controlling intraocular pressure and normal aqueous humor physiology. New and unique pharmacologic manipulations of aqueous humor dynamics may be possible with the potential for the demonstration of new therapies for glaucoma. Mechanisms responsible for drug-induced alterations in intraocular pressure will be investigated. Noninvasive measurements of outflow facility, episcleral venous pressure and aqueous humor flow will be performed. Invasive determination of aqueous humor flow, total outflow facility, and ocular blood flow and volume, will be measured. Biochemical determinations include measurement of aqueous humor protein, ascorbate, and cyclic AMP concentration. Aqueous humor dynamic studies are performed following topical, systemic, intracameral, or intravitreal administration. Neuropeptides to be investigated include vasopressin and neuropeptide Y. Attention is directed to determining the specificity and the interaction of these agents with classical neurotransmitters. In addition, in vitro studies of the effects of neuropeptides as regulators/modifiers on anterior segment smooth muscles will be performed to provide additional information on these naturally occurring peptide hormones. The molecular probes amiloride (sodium transport inhibitor) and apamin (potassium transport inhibitor) will be investigated for their effect on intraocular pressure.