Akt (Protein Kinase B) subtypes in retinal ischemic postconditioning

Abstract

INTRODUCTION: We have previously described enhancement of recovery in a rat model of retinal ischemia by ischemic post-conditioning using transient elevation of intraocular pressure after ischemia. We previously demonstrated involvement of protein kinase B (Akt) in this form of neuroprotection. In this study, we examined the hypothesis that specific Akt subtypes underlie this phenomenon. METHODS: Ischemia was produced by elevation of intraocular pressure above systolic arterial blood pressure for 55 min in anesthetized adult Wistar rats. Post-conditioning was produced by 8 min elevation of intraocular pressure to the same level at 5 min after reperfusion following ischemia. Interfering RNA (siRNA) to Akt subtypes 1, 2, or 3, or non-silencing siRNA was injected into the vitreous 6 h prior to ischemia. Recovery was assessed using electroretinography (ERG) and histological examination of 5-micron thick retinal paraffin embedded sections. RESULTS: Injection of interfering RNA to Akt subtype 1 significantly decreased the post-conditioning ischemia protective effect as reflected by decreased recovery of the electroretinogram b wave and oscillatory potentials (OPs) (Figure).[figure1]CONCLUSIONS: The results show the involvement of specific Akt subtypes in the intriguing and clinically relevant phenomenon of post-ischemic conditioning. Enhancing expression of these subtypes may be a viable means to decrease neuronal injury after ischemia.