Excitotoxicity-associated p53 expression in adult rat retina is mediated by calpain activity but not by Cl- influx

Abstract

We have previously demonstrated an important role of influx of Cl - rather than Ca2+ in acute excitotoxicity in adult rat retina. As p53 has been implicated in delayed apoptotic cell death, here we examined the appearance of p53 immunoreactivity in a rat eyecup preparation. Kainate induced p53 expression in a subpopulation of ganglion cells and other cells in the ganglion cell layer. Application of a calpain inhibitor, but not reduction of extracellular Cl-, markedly inhibited kainate-induced p53 expression. The results suggest that, in contrast to acute excitotoxicity, delayed excitotoxicity in retinal neurons is mediated by Ca2+- dependent processes, including calpain activation. ©2009 The Japanese Pharmacological Society.