Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (2): 357-363.doi: 10.4103/1673-5374.346545

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

Wei-Tao Yan1, #, Wen-Juan Zhao1, #, Xi-Min Hu2, Xiao-Xia Ban1, Wen-Ya Ning3, Hao Wan1, Qi Zhang1, *, Kun Xiong1, 4, 5 *   

  1. 1Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 3Department of Human Resources, Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China; 4Hunan Key Laboratory of Ophthalmology, Changsha, Hunan Province, China; 5Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, Hainan Province, China
  • Online:2023-02-15 Published:2022-08-08
  • Contact: Kun Xiong, MD, xiongkun2001@163.com; Qi Zhang, MD, zhangqi2014@csu.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81772134, 81971891, 82172196, 81571939 (all to KX); the Key Laboratory of Emergency and Trauma (Hainan Medical University) of Ministry of Education, No. KLET-202108 (to KX); the Fundamental Research Funds for the Central Universities of Central South University of China, No. 2020zzts218 (to WTY); Hunan Provincial Innovation Foundation for Postgraduate of China, No. CX20200116 (to WTY). 

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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.

Key words: 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