Studies on the control of aqueous humor dynamics using selected antiglaucoma and autonomic drugs

Abstract

A blue dextran perfusion method for in vivo aqueous humor dynamic studies in the anesthetized cat eye was developed. The rates of aqueous humor formation and aqueous humor outflow were monitored simultaneously and instantaneously at a constant intraocular pressure. The validity of this method was verified with three antiglaucoma drugs, acetazolamide, pilocarpine and L-timolol. Data variability from this method was found to be less than that from the conventional ('14)C-inulin perfusion method. The effects of 13 autonomic agents on aqueous humor formation and outflow were studied using this method. With the exception of norepinephrine, which only decreased outflow, and L-timolol, which only decreased formation, both aqueous humor formation and aqueous humor outflow were reduced by all adrenergic agents tested. It is concluded that the ocular hypotensive action of adrenergic agents on the feline eye occurs when the inhibition of aqueous humor formation exceeds the inhibition of aqueous humor outflow. Aqueous humor outflow was slightly decreased within a short time after the intracameral infusion of N-demethylated carbachol, then it was increased. Aqueous humor formation was not affected. This confirms the hypothesis that the mechanism of cholinergic agonists in lowering intraocular pressure is due to a facilitation of aqueous humor outflow. D-Timolol was found to be as effective as L-timolol in inhibiting aqueous humor formation. No effect on aqueous humor outflow was found. This indicates that L-timolol might decrease aqueous humor formation by mechanisms other than (beta)-adrenergic blockade. No appreciable inhibition of carbonic anhydrase was found with L-timolol. It is concluded that the action mechanism of timolol to inhibit aqueous humor formation differs from that of carbonic anhydrase inhibitors. Actions of prostaglandin E(,2) on aqueous humor dynamics were not effectively antagonized by L-timolol. This indicates that the ocular hypotensive effect of timolol is unrelated to the antagonism of prostaglandin.