The specific aims are: 1) to measure noninvasively aqueous humor formation rate in primates using fluorophotmetry, 2) to determine the influence of topical adrenergic drugs and role of endogenous adrenergic mediators on aqueous humor formation rate, and 3) to study loss of drug responsiveness in primates undergoing chronic drug treatment. Aqueous humor formation rate will be determined by measuring the anterior chamber elimination coefficient and anterior chamber volume. All measurements of ocular fluorescence will be made with a sensitive fluorophotometer developed specifically for this purpose. The methodology involves initially delivering fluorescein iontophoretically to the corneal stroma and measuring its mass in situ. Fluorescein concentration in the cornea and the aqueous humor will be measured hourly to determine the time course of the exit of fluorescein. A least-squares, computer generated best fit of the data will be used to calculate the anterior chamber elimination coefficient based on a two compartment pharmacokinetic model. The anterior chamber will be photographed with a slitlamp and the dimensions of central, sagittal profiles will be quantitated planimetrically to determine volume. Anesthetized animals will be used initially to permit comparison with results obtained using the invasive methods, constant pressure perfusion and dextran-labeled dye dilution. Subsequent experiments will be performed in unanesthetized, conditioned animals seated in a primate chair. Pharmacological studies will include the effects of Beta-adrenergic agonists and antagonists (eg. epinephrine and timolol) in normal animals and in the same animals following unilateral sympathetic denervation. The rate of formation will be measured in other animals before and after bilateral adrenatectomy and drug effects determined. Various drugs will be continued chronically to determine if their efficacy for reducing aqueous humor formation decreases in the primate model as in glaucoma patients. The long term objectives are: 1) use fluorophotometry to develop a conscious primate model for studying clinical problems associated with aqueous humor formation, 2) study the physiology of formation using adrenergic drugs and determine whether adrenergic stimulation influences normal inflow, and 3) study the loss of hypotension action of adrenergic drugs with chronic use.
| Murray, D L; Bartels, S P (1993) The relationship between aqueous humor flow and anterior chamber protein concentration in rabbits. Invest Ophthalmol Vis Sci 34:370-6 |
| Freddo, T F; Bartels, S P; Barsotti, M F et al. (1992) Morphologic correlations with fluorophotometric data from monkey eyes with anterior uveitis. Invest Ophthalmol Vis Sci 33:1642-9 |
| Barsotti, M F; Bartels, S P; Freddo, T F et al. (1992) The source of protein in the aqueous humor of the normal monkey eye. Invest Ophthalmol Vis Sci 33:581-95 |
| Liu, J H; Dacus, A C; Bartels, S P (1991) Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits. Invest Ophthalmol Vis Sci 32:2178-83 |
| Freddo, T F; Bartels, S P; Barsotti, M F et al. (1990) The source of proteins in the aqueous humor of the normal rabbit. Invest Ophthalmol Vis Sci 31:125-37 |
| Barsotti, M F; Bartels, S P; Kamm, R D et al. (1990) Background-protein effects on fluorophotometric data. Invest Ophthalmol Vis Sci 31:2046-50 |
| Bartels, S P; Pawlowski, A M (1990) Chronic electrical stimulation of sympathetic nerves: effects on blood-aqueous barrier. Curr Eye Res 9:927-34 |
| Liu, J H; Dacus, A C; Bartels, S P (1989) Thyrotropin releasing hormone increases intraocular pressure. Mechanism of action. Invest Ophthalmol Vis Sci 30:2200-8 |
| Bartels, S P (1988) Aqueous humor flow measured with fluorophotometry in timolol-treated primates. Invest Ophthalmol Vis Sci 29:1498-504 |
| Higginbotham, E J; Lee, D A; Bartels, S P et al. (1988) Effects of cyclocryotherapy on aqueous humor dynamics in cats. Arch Ophthalmol 106:396-403 |
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