Prothymosin-α plays a defensive role in retinal ischemia through necrosis and apoptosis inhibition

Abstract

Prothymosin-α (ProTα) causes a switch in cell death mode from necrosis to neurotrophin-reversible apoptosis in primary cultured cortical neurons. In the present study, post-ischemic administration (3 or 24h, intravenously) of recombinant mouse ProTα without neurotrophins completely prevented ischemia-induced retinal damage accompanying necrosis and apoptosis, as well as dysfunction assessed by electroretinogram. Treatments with anti-erythropoietin (EPO) or brain-derived neurotrophic factor (BDNF) immunoglobulin G (IgG) reversed ProTα-induced inhibition of apoptosis. ProTα upregulated retinal EPO and BDNF levels in the presence of ischemia. Moreover, intravitreous administration of anti-ProTα IgG or an antisense oligodeoxynucleotide for ProTα accelerated ischemia-induced retinal damage. We also observed that ischemia treatment caused a depletion of ProTα from retinal cells. Altogether, these results suggest that the systemic administration of ProTα switches ischemia-induced necrosis to apoptosis, which in turn is inhibited by neurotrophic factors upregulated by ProTα and ischemia. ProTα released upon ischemic stress was found to have a defensive role in retinal ischemia.