The project aims are: 1) to define the pharmacological profile of the primate aqueous humor formation and drainage apparatus in terms of its physiological and morphological responses; 2) to define and to understand the pathophysiology of the functional and morphological toxicity of currently used antiglaucoma drugs. The influence of drugs on aqueous humor formation and drainage in the living monkey eye will be studied using invasive perfusion techniques and noninvasive fluorophotometric techiques. In some eyes, the ciliary muslce will be disconnected from the scleral spur so that drug effects on the function of the trabecular meshowrk will not be distorted by dru-induced changes in ciliary muscle tone. Other eyeswill be parasympathetically denervated via ciliary ganglionectomy to assess the role of intact cholinergic innvervation in mediating drug responses. The effects of cholinergics, adrenergics, cyclic nucleotides, hormones, peptides, prostaglandings, cytochalasins, chelators, cannabinoids, ionophores, carbonic anhydrase inhibitors, and corticosteroids will be assessed using putative agonists, antagonists, mdiators, and metabolites, and interactions among different drug classes will be sought. The morphological basis for any drug-induced functional changes will be studied electron microscopically. These studies should improve our understanding of the basic mechanisms of aqueouos humor formation and drainage in the primate eye, and thus may enhace our knowledge of the pathophysiology of human glaucoma and contribute to new pharmacological approaches to its treatment.
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