May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Evidence That High Intraocular Pressure (IOP)-Induced Retina Ischemia/Reperfusion Modulates PI-3K/Akt Pro-Survival Pathway in Rat
Author Affiliations & Notes
  • R. Russo
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • C. Nucci
    Ophthalmology, University of Rome Tor Vergata, Rome, Italy
    IRCCS C. Mondino-Tor Vergata center for experimental neuropharmacology, Rome, Italy
  • A. Ciociaro
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • F. Cavaliere
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • A. Cerulli
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
    Ophthalmology, University of Rome Tor Vergata, Rome, Italy
  • E. Fazzi
    IRCCS Fondazione Istituto Neurologico "C. Mondino", Pavia, Italy
  • G. Bagetta
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • M. Corasaniti
    Pharmacobiological Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
  • Footnotes
    Commercial Relationships  R. Russo, None; C. Nucci, None; A. Ciociaro, None; F. Cavaliere, None; A. Cerulli, None; E. Fazzi, None; G. Bagetta, None; M. Corasaniti, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5511. doi:https://doi.org/
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      R. Russo, C. Nucci, A. Ciociaro, F. Cavaliere, A. Cerulli, E. Fazzi, G. Bagetta, M. Corasaniti; Evidence That High Intraocular Pressure (IOP)-Induced Retina Ischemia/Reperfusion Modulates PI-3K/Akt Pro-Survival Pathway in Rat. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5511. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : to investigate the role of self-defense mechanisms mediated by Akt, a serine/threonin kinase with pro-survival and anti-apoptotic activities (Franke et al., 2003, Oncogene, 22:8983-98), in a model of RGCs death induced in vivo by high intraocular pressure (IOP).

Methods: : retina ischemia was induced in the right eye of adult, male, Wistar rat (250 g) by acutely increasing the intraocular pressure (IOP) (see Osborne et al., 2004, Prog Ret Eye Res; 23:91-147). Expression and activity of Akt and its downstream targets were studied by western blotting and immunofluorescence. NMDA antagonists and PI-3K inhibitors were administered intravitreally to test their effect on Akt activation.

Results: : retina ischemia induces Akt deactivation (dephosphorylation) that correlates with the activation of the pro-apoptotic protein GSK-3beta. Akt activity increases within 1 hour of reperfusion, is sustained after 6 hours and gradually returns to basal levels after 24 hours. Activation of Akt during reperfusion relays on PI-3K function, since pharmacological inhibition of this enzyme prevents the increase of Akt phosphorylation observed at 1 hour of reperfusion. Intravitreal injection of NMDA antagonists do not affect Akt phosphorylation during ischemia/reperfusion.

Conclusions: : the PI3K/Akt pathway is modulated under retina ischemia/reperfusion showing that endogenous survival factors are strongly activated in response to injury. Activation of this pro-survival pathway is concomitant but independent from the activation of glutamate receptors which occurs as part of the excitotoxic death of RGCs during retina ischemia/reperfusion (see Nucci et al., 2005, Neurotoxicology, 26: 935-941).

Keywords: excitatory amino acid receptors • signal transduction • ganglion cells 
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