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

We have previously demonstrated an important role of influx of Cl(-) rather than Ca(2+) 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 Ca(2+)-dependent processes, including calpain activation.