Vol. 288, Issue 2, 838-842, February 1999

Timolol Effects on Aqueous Humor Dynamics in Eyes of Anesthetized Rats¹

Robin V. Searles, Vladimir Shikher, Carey D. Balaban and Walter B. Severs

Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania (R.V.S., W.B.S.) and Department of Otolaryngology, The Eye and Ear Institute, University of Pittsburgh, Pittsburgh, Pennsylvania (V.S., C.D.B.)

Anterior chambers of the eyes of male rats were cannulated under pentobarbital anesthesia for intracameral infusions of balanced salt solution (BSS) and intraocular pressure (IOP) recording. Blood pressure was recorded from a femoral artery. IOP was recorded during a 2-h intracameral infusion composed of a constant component (0.05 µl/min) and a periodic component (0.25 µl/min), cycling at 4 min on and then 4 min off. After a 20-min baseline period, 1 drop of timolol (0.5%) or BSS was applied to the cornea and repeated 1 h later. Intracameral infusions of BSS and 0.05% timolol were also compared. Topical timolol slightly delayed the BSS-induced IOP rise (p < .05). Complex demodulation and the estimated gain parameter of a second-order transfer function fit to the periodic responses revealed that topical timolol also reduced (p < .05) passive outflow resistance. Intracameral timolol markedly delayed the BSS-induced rise in IOP. Initially, timolol decreased both outflow impedance and nonresistive components (p < .05) of IOP, but these effects dissipated by 2 h when IOPs were similar. In all experiments, within-group blood pressure was unchanged. Topical and intracameral timolol have different effects on IOP. The data support the opinion that, in vivo, timolol acts at -receptors that control both outflow impedance and nonresistive mechanisms, probably vascular, to lower IOP.