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Research ArticleCELLULAR AND MOLECULAR

α2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia

John E. Donello, Edwin U. Padillo, Michelle L. Webster, Larry A. Wheeler and Daniel W. Gil
Journal of Pharmacology and Experimental Therapeutics January 2001, 296 (1) 216-223;
John E. Donello
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Edwin U. Padillo
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Michelle L. Webster
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Larry A. Wheeler
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Daniel W. Gil
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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

  • 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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Journal of Pharmacology and Experimental Therapeutics: 296 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 296, Issue 1
1 Jan 2001
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Research ArticleCELLULAR AND MOLECULAR

α2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia

John E. Donello, Edwin U. Padillo, Michelle L. Webster, Larry A. Wheeler and Daniel W. Gil
Journal of Pharmacology and Experimental Therapeutics January 1, 2001, 296 (1) 216-223;

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Research ArticleCELLULAR AND MOLECULAR

α2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia

John E. Donello, Edwin U. Padillo, Michelle L. Webster, Larry A. Wheeler and Daniel W. Gil
Journal of Pharmacology and Experimental Therapeutics January 1, 2001, 296 (1) 216-223;
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