PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

Abstract

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis, apoptosis, and necroptosis, which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases. Although our previous literature mining study suggested that PANoptosis might occur in neuronal ischemia/reperfusion injury, little experimental research has been reported on the existence of PANoptosis. In this study, we used in vivo and in vitro retinal neuronal models of ischemia/reperfusion injury to investigate whether PANoptosis-like cell death (simultaneous occurrence of pyroptosis, apoptosis, and necroptosis) exists in retinal neuronal ischemia/reperfusion injury. Our results showed that ischemia/reperfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo. Ischemia/reperfusion injury also significantly upregulated caspase-1, caspase-8, and NLRP3 expression, which are important components of the PANoptosome. These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

Keywords

• apoptosis; gasdermin-d (gsdmd); ischemia/reperfusion; mixed lineage kinase domain-like protein (mlkl); necroptosis; nod-like receptor protein 3 (nlrp3); panoptosis; pyroptosis; receptor-interacting protein kinase 3 (ripk3); retinal neuron