This project will characterize: functional/structural responses of the monkey aqueous human formation/drainage apparatus to pharmacologic probes; pathophysiology of deviations from normal function/structure produced by long-term antiglaucoma drug treatment; the role of cholinergic/adrenergic innervation in normal function, structure, their responses to pharmacologic agents, and deviations from normal produced by long-term antiglaucoma drug treatment; cytoskeletal, cell junctional, and extracellular matrix interactions of human trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes; the effect on aqueous outflow of relevant proteins encoded by genes delivered to the anterior chamber. Aqueous formation and drainage will be determined by perfusion and fluorophotometry. Accommodation will be stimulated by cholinergic agonists or a midbrain electrode and determined by coincidence refractometry. The ciliary muscle will be disinserted to identify primary drug effects on the trabecular meshwork. Parasympathetic denervation will be induced by ciliary ganglionectomy or panretinal photocoagulation, sympathetic denervation by superior cervical ganglionectomy. The effects of cholinergics, adrenergics, cyclic nucleotides, G-protein activators, hormones, peptides, prostaglandins, cytoskeletal agents, calcium channel blockers, cannabinoids, ionophores, carbonic anhydrase inhibitors, corticosteroids, and other compounds will be assessed in previously untouched, autonomically 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 drug classes sought. Aqueous formation and drainage will be evaluated after injection of vectors containing genes whose products may affect aqueous humor dynamics. In vitro responses of trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes will be studied using immunohistochemistry to examine cytoskeletal and cell junctional changes. Structural parameters in the meshwork and ciliary muscle/processes of intact eyes will be evaluated by light/electron microscopy, immunohistochemistry and quantitative morphometry.
Showing the most recent 10 out of 211 publications
