Abstract
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.
Footnotes
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Send reprint requests to: John E. Donello, Ph.D., Department of Biological Sciences, Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612. E-mail: Donello_john{at}allergan.com
- Abbreviations:
- ERG
- electroretinogram/electroretinography
- RGC
- retinal ganglion cell
- LC/MS/MS
- liquid chromatography/mass spectrometry/mass spectrometry
- PTI
- prior to ischemia
- Received June 30, 2000.
- Accepted September 8, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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