The objectives are to determine the basic processes underlying aqueous humor formation and to determine and describe the modification of these processes by various drugs.
The specific aims are: a) to determine the effects of drugs on aqueous dynamics in albino and pigmented rabbit and rhesus monkey eyes. This will be achieved by measuring intraocular pressure in both species, and with fluorimetry in rabbits and measurement of total outflow facility in monkeys. Drugs to be employed include the stereoisomers of adrenergic compounds, as well as a variety of specific antagonists in order to delineate the various receptor populations; b) to measure regional ocular, and optic nerve, blood flow after either acute or chronic drug treatment. Radioactive microspheres will be used for ocular blood flow and either iodoantipyrine or deoxyglucose for optic nerve blood flow. Drugs to be used include adrenergic compounds and drugs used in ophthalmic practice; c) to measure ciliary epithelial permeability characteristics in the the aniridic and normal monkey eye. In aniridic eyes, anterior chamber perfusion will be made with a variety of solutes and the rise in intraocular pressure used to determine permeability. In normal eyes, intravenous infusion of radiolabelled solutes will be made with samples of anterior and posterior chamber fluid made also to determine normal and drug-affected permeability; d) to measure prostaglandin and prostacyclin formation by ocular tissues following extracapsular lens removal in rabbits, both in the presence and absence of topical indomethacin treatment. These studies will define whether or not autocoids are inhibited locally or only in the anterior segment in relation to events at the macula; e) determine the effects of drugs and chemicals on the intracellular electrical potential difference of ciliary epithelial cells (using microelectrodes), and the transmembrane electrical characteristics and ion fluxes using an in vitro iris-ciliary body preparation; and f) Determine the effects on iris vasculature, blood-aqueous barrier permeability, and other parameters of ocular inflammation (e.g., PMN influx; aqueous ascorbic acid hydrogen peroxide concentration) after in vivo generation of oxygen free radicals, using PMNs activated with zymosan, and after anterior chamber injection of hydrogen peroxide in the rabbit eye. These experiments will be made in normal rabbits or in those treated with 3-amino-triazole to suppress native catalase.
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