Effects of α2-Adrenergic Agonists on Lipopolysaccharide-induced Aqueous Flare Elevation in Pigmented Rabbits

Abstract

Purpose: To evaluate the effects of the α 2-adrenergic agonists (clonidine, apraclonidine, and guanfacine) on lipopolysaccharide (LPS)-induced aqueous flare elevation in pigmented rabbits. Methods: Anterior uveitis was induced with an intravenous injection of LPS (0.5 μg/kg) in an ear vein. The reproducibility of experimental uveitis induced by LPS (0.5 μg/kg) was also determined. Clonidine (0.01, 0.05, 0.25, or 1%), apraclonidine (1%), or guanfacine (1%) was topically instilled in the right eye 30 and 5 minutes before and 30 minutes after LPS application (N = 6 animals, respectively). Clonidine (0.25%) was topically administered three times at 30-minute intervals from 240 or 120 minutes before, or 120 or 240 minutes after LPS application (N = 6 animals, respectively). Then 1 mg/kg of yohimbine was injected into an ear vein 30 minutes before each topical three-time instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% (N = 6 animals, respectively). Aqueous flare was measured with a laser flare-cell meter. Aqueous flare elevation was expressed as the area under the curve (AUC) in arbitrary units. Rabbits received the first LPS intravenous injection, and the control values of the AUC were obtained. Three months later, the α 2-agonist and the second LPS administration were given to the same animals. Results: The AUCs (5,184 ± 1,255 units) after the first application of LPS were similar to those (5,033 ± 1,290) after the second application 3 months after the first administration. Topical instillation of clonidine inhibited LPS-induced aqueous flare elevation in a dose-dependent manner (0.01–0.25%). Topical instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% inhibited LPS-induced aqueous flare elevation by 98 ± 2.0% (mean ± SD), 86 ± 14% and 94 ± 5.7%, respectively. Pretreatment with intravenous yohimbine prevented the inhibitory effect on flare elevation induced by each agent. Conclusion: The present findings suggested that topical instillation of some α 2-agonists may have an inhibitory effect on ocular inflammation, which is mediated in part by α 2-receptors.