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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.
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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).
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.
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.
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).
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