Effects of alpha(2)-adrenergic agonists on lipopolysaccharide-induced aqueous flare elevation in pigmented rabbits

Purpose: To evaluate the effects of the alpha (2)-adrenergic agonists (clon idine, apraclonidine, and guanfacine) on lipopolysaccharide (LFS)-induced a queous flare elevation in pigmented rabbits. Methods: Anterior uveitis was induced with an intravenous injection of LPS (0.5 mug/kg) in an car vein. The reproducibility of experimental uveitis in duced by LPS (0.5 mug/kg) was also determined. Clonidine (0.01, 0.05, 0.25, or 1%), apraclonidine (1%), or guanfacine (1%)was topically instilled in t he right eye 30 and 5 minutes before and 30 minutes after LPS application ( N = 6 animals, respectively). Clonidine (0.25%) was topically administered three rimes at 30-minute intervals from 240 or 120 minutes before, or 120 o r 240 minutes after LPS application (N = 6 animals, respectively). Then 1 m g/kg of yohimbine was injected into an ear vein 30 minutes before each topi cal 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 t he curve (AUC) in arbitrary units. Rabbits received the first LPS intraveno us injection, and the control values of the AUC were obtained. Three months later, the alpha (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 LP S were similar to those (5,033 +/- 1,290) after the second application 3 mo nths after the first administration. Topical instillation of clonidine inhi bited LPS-induced aqueous flare elevation in a dose-dependent manner (0.01- 0.25%). Topical instillation of clonidine 1%, apraclonidine 1% or guanfacin e 1% inhibited LPS-induced aqueous flare elevation by 98 +/- 2.0% (mean +/- SD), 86 +/- 14% and 94 +/- 5.7%, respectively. Pretreatment with intraveno us yohimbine prevented the inhibitory effect on flare elevation induced by each agent. Conclusion: The present findings suggested that topical instillation of som e alpha (2)-agonists may have an inhibitory effect on ocular inflammation, which is mediated in part by alpha (2)-receptors. (C) 2001 Japanese Ophthal mological Society.