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Aqueous humor production is a metabolically active process sustained by the delivery of oxygen and nutrients and removal of metabolic waste by the ciliary circulation. This article describes our investigations into the relationship between ciliary blood flow and aqueous humor production. The results presented indicate that there is a dynamic relationship between ciliary blood flow and aqueous humor production, with production being blood flow independent above a critical level of perfusion, and blood flow dependent below it. The results also show that the plateau portion of the relationship shifts up or down depending on the level of secretory stimulation or inhibition, and that oxygen is one critical factor provided by ciliary blood flow. Also presented is a theoretical model of ocular hydrodynamics incorporating these new findings.

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Purpose: AR-13324 is a potential new drug for the treatment of patients with glaucoma that has been shown to lower intraocular pressure (IOP) by increasing trabecular outflow facility and decreasing aqueous production. The present study tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous pressure (EVP).Methods: In Dutch Belted (DB) rabbits (n=11), arterial pressure (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured invasively. Animals were dosed with AR-13324 (0.04%, topical, n=6) once daily for 3 days. On day 3, the animals were anesthetized, and then, measurements were obtained before dosing with AR-13324 or vehicle (n=5) and for 3 h after dosing. The data (mean±standard error of the mean) were analyzed by repeated measures ANOVA with post hoc testing. Retrospective baseline data from prior similar studies in New Zealand White rabbits were also compiled.Results: Baseline values were as follows: AP, 101±3 mmHg; IOP; 33±3 mmHg; EVP, 16±1 mmHg; BFcar, 41±4 mL/min; and HR, 330±6 bpm. Three hours after AR-13324 dosing, IOP was reduced by 39%±7% (P<0.001) and EVP decreased by 35%±4% (P<0.05); after vehicle dosing, IOP was reduced by 24%±4% (P<0.05) and EVP increased by 25%±5% (P<0.05). AP, BFcar, and HR were unchanged.Conclusions: AR-13324 produces statistically significant lowering of EVP in DB rabbits. In addition, the baseline values for AP, IOP, EVP, BFcar, and HR in the DB rabbit are higher than those previously reported in the New Zealand rabbit.

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