Modulation of pro-survival and death-associated pathways under retinal ischemia/reperfusion: Effects of NMDA receptor blockade

R. Russo, F. Cavaliere, L. Berliocchi, C. Nucci, M. Gliozzi, C. Mazzei, C. Tassorelli, M. T. Corasaniti, D. Rotiroti, G. Bagetta, L. A. Morrone

Research output: Contribution to journalArticlepeer-review

Abstract

Loss of retinal ganglion cells occurs in a variety of pathological conditions, including central retinal artery occlusion, diabetes and glaucoma. Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3β followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3β. Under these experimental conditions, retinal ischemia induced the expression of Bad, a pro-apoptotic protein, member of the Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were minimized by intravitreal administration of the NMDA receptor antagonist, MK801, that reduced the expression of Bad and significantly increased Akt phosphorylation. In conclusion, our present results contribute to unravel the mechanisms underlying retinal damage by high IOP-induced transient ischemia in rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the observed reduced expression of Bad in the neuroprotection afforded by MK801.

Original languageEnglish
Pages (from-to)1347-1357
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number5
DOIs
Publication statusPublished - Dec 2008

Keywords

  • Akt
  • Excitoxicity
  • MK801
  • PI3K
  • Retinal ischemia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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