This project aims to (1) characterize the pharmacologic profiles of the primate aqueous humor formation/drainage apparatus by determining their functional and structural responses to pharmacologic probes; (2) characterize and determine the pathophysiology of deviations from normal function and structure produced by long-term administration of present and putative antiglaucoma drugs; (3) determine the role of cholinergic and adrenergic innervation in (a) maintaining normal function and structure, (b) mediating normal functional and structural responses to pharmacologic agents, and (c) mediating deviations from normal produced by long-term administration of present and putative antiglaucoma drugs; (4) delineate the mechanism by which argon laser trabeculoplasty increases aqueous outflow facility. Aqueous humor formation and drainage will be determined in the living monkey eye using invasive perfusion techniques and noninvasive fluorophotometric techniques. Accommodation, which provides a noninvasive measure of ciliary muscle contractility, will be determined by coincidence refractometry and stimulated centrally by an electrode implanted in the Edinger-Westphal nucleus. In some eyes, the ciliary muscle will be disconnected from the scleral spur so that drug effects on the trabecular meshwork will not be distorted by drug-induced changes in ciliary muscle tone. Parasympathetic denervation will be induced surgically by ciliary ganglionectomy/post-ganglionic ciliary neurectomy and perhaps pharmacologically by cholinergic neurotoxins. Sympathetic denervation will be induced surgically by superior cervical ganglionectomy and perhaps pharmacologically by 6-hydroxydopamine. The effects of cholinergics, adrenergics, cyclic nucleotides, hormones, peptides, prostaglandins, cytochalasins, chelators, cannabinoids, ionophores, carbonic anhydrase inhibitors, and corticosteroids will be assessed using putative agonists, antagonists, mediators, and metabolites, and interactions among different drug classes will be sought. Structural parameters will be determined by light and electron microscopy. Cholinergic and adrenergic receptor subtypes will be quantified by ligand binding techniques. These studies may enhance our knowledge of the pathophysiology of human glaucoma and its therapy and contribute to new pharmacological approaches to glaucoma treatment.
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