Beta-Blocker Modulation of Aqueous Humor Production

Rittenhouse, Kay

Abstract

application). Research to elucidate the mechanisms of and treatment approaches for glaucoma is required to reduce the incidence and improve the prognosis of this disease, which results in progressive damage to the optic nerve. The incidence of high intra-ocular pressure (IOP), a risk factor for glaucoma, increases with age; for populations > 40 years of age, the incidence is between 4-10% (Figeret, et a1, 1989). Treatment approaches to reduce high IOP include drugs which modulate aqueous humor (AH) inflow and/or outflow. Although topical beta-adrenergic antagonists are used routinely for the treatment of primary open angle glaucoma, conflicting results have been obtained in evaluating the pharmacodynamics of IOP reduction. Further investigation and elucidation of the pharmacodynamics of these antiglaucoma agents is warranted. A number of technologies have been used to examine AH formation and turnover. The goal of this research project is to provide a method for the accurate assessment of the pharmacokinetics and pharmacodynamics of topically administered beta-- adrenergic antagonists in the reduction of aqueous humor (AH) production. This project will test the hypothesis that microdialysis sampling of AH for endogenous concentrations of ascorbate can be used to estimate the basal and perturbed AH turnover rate following regionally administered beta-adrenergic antagonists. This project also will examine possible beta-adrenergic perturbation of the rate of ascorbate secretion into AH. Microdialysis has been used for the regional sampling of brain, blood, liver (Kurata, et al., 1995), muscle, kidney (Ekstrom, et al., 1995), joint (Sluka, et al., 1994), ocular vitreous (Ben-Nun, et al., 1989), anterior chamber AH (Rittenhouse, et al., 1997 in press; Sato, et al., 1996), and retina (Louzada-Junior, et al. 1992). This technology offers important advantages over present approaches. By this approach, it is anticipated that further progress will be made in the elucidation of the effect of beta-adrenergic antagonist on AH production and, as a consequence, intraocular pressure lowering.