This project will characterize: (1) the pharmacologic profiles of the monkey aqueous humor formation/ drainage apparatus by determining their functional/structural responses to pharmacologic probes; (2) the pathophysiology of deviations from normal function/structure produced by long-term antiglaucoma drug treatment; (3) the role of cholinergic/adrenergic innervation in (a) maintaining normal function/structure, (b) mediating normal functional/structural responses to pharmacologic agents, and (c) mediating deviations from normal produced by long-term antiglaucoma drugs treatment. Aqueous humor formation and drainage will be determined by perfusion and fluorophotometry. Accommodation, stimulated by cholinergic agonists or a midbrain electrode, will be determined by coincidence refractometry. The ciliary muscle will be disconnected from the scleral spur to distinguish primary drug effects on the trabecular meshwork from indirect effects mediated by the ciliary muscle. Parasympathetic denervation will be induced by ciliary ganglionectomy or panretinal photocoagulation. Sympathetic denervation will be induced by superior cervical ganglionectomy. The effects of cholinergics, adrenergics, cyclic nucleotides, G-protein activators, hormones, peptides, prostaglandins, cytochalasins, chelators, calcium channel blockers, cannabinoids, ionophores, carbonic anhydrase inhibitors, corticosteroids, and other compounds will be assessed in previously untouched, sympathetically/ parasympathetically denervated, ciliary muscle disinserted, and long-term antiglaucoma drug-treated eyes. Agonists, antagonists, mediators, metabolites, and protein and RNA synthesis inhibitors will be used, and interactions among different drug classes will be sought. Structural parameters in the meshwork and ciliary muscle/processes will be evaluated by light/electron microscopy, immunohistochemistry and quantitative morphometry. Cholinergic/adrenergic receptor subtypes will be identified, quantified and localized by ligand binding, autoradiography and in situ hybridization in untouched eyes and following the various perturbations.
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