Adenosine protects cultured retinal neurons against NMDA–induced cell death through A1 receptors

Abstract

Abstract: : Purpose:To determine whether adenosine can protect cultured retinal neurons from the NMDA–induced neurotoxicity, and to determine whether agonists and antagonists of its receptors also have a protective effect. Methods:Cultured retinal neurons obtained from fetal Wistar rats (gestational age 18–19 days) were maintained for 10–11 days. They were exposed to NMDA (1.0 mM) for 10 minutes with or without adenosine or to NMDA with adenosine receptor agonists or antagonists. Neuronal death was assessed by the trypan–blue exclusion method 1 and 24 hours after exposure. Results:Adenosine at doses higher than 0.1 µM significantly protected (P <0.05, Dunnett) primary cultured fetal rat retinal neurons from apoptotic and/or necrotic death induced by NMDA (1.0 mM). The protective effect of adenosine (10 µM) assessed at 24 hours after NMDA was lost by simultaneous treatment with A1 receptor antagonist, but not with A2 receptor antagonist. A1 receptor agonist mimicked the effects by adenosine, but A2 receptor agonist and 8 Br–cyclic AMP had no effect on cell viability. Conclusions:Adenosine and its A1 receptor can protect retinal neurons in culture against the NMDA–induced cell death.

Keywords: adenosine • neuroprotection • retinal culture