RT Journal Article SR Electronic T1 α2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 216 OP 223 VO 296 IS 1 A1 John E. Donello A1 Edwin U. Padillo A1 Michelle L. Webster A1 Larry A. Wheeler A1 Daniel W. Gil YR 2001 UL http://jpet.aspetjournals.org/content/296/1/216.abstract AB Recent studies have suggested that α2-adrenergic agonists prevent neuronal cell death in a number of animal models, although the mechanism of α2-neuroprotection remains unclear. In a retinal ischemia model, the α2-specific agonist brimonidine (1 mg/kg i.p.) preserves approximately 80% of the electroretinogram (ERG) b-wave. The protective effect of brimonidine is completely blocked by coadministration of the α2- antagonist rauwolscine. Brimonidine treatment preserves the ERG b-wave if animals are treated 1 or 3 h before ischemia, but has no effect if it is injected during ischemia. The 3-h pretreatment effect is blocked by i.v. injection of rauwolscine 2 h later (1 h before ischemia). A comparison of vitreous humor glutamate levels between untreated and brimonidine-treated eyes shows that 1) after ischemia, glutamate levels rise 2- to 3-fold in the untreated animals, and 2) glutamate levels in the brimonidine-treated animals are comparable to the nonischemic controls. Hence, the mechanism for brimonidine-mediated protection in the retinal ischemia model requires activation of the α2-adrenergic receptors immediately before and during ischemia. These data suggest that activation of the α2-adrenergic receptor may reduce ischemic retinal injury by preventing the accumulation of extracellular glutamate and aspartate. The American Society for Pharmacology and Experimental Therapeutics