The IL-33/ST2 Axis Protects Retinal Ganglion Cells by Modulating the Astrocyte Response After Optic Nerve Injury  

作　　者：Zhigang Qian Mengya Jiao Na Zhang Xuhuan Tang Shiwang Liu Feng Zhang Chenchen Wang Fang Zheng 

机构地区：[1]Department of Immunology,School of Basic Medicine,Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Huazhong University of Science and Technology,Wuhan,430030,China [2]Department of Ophthalmology,Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Science,Xiangyang,441000,China [3]National Demonstration Center for Experimental Basic Medical Education,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,China [4]Key Laboratory of Organ Transplantation,Ministry of Education,NHC Key Laboratory of Organ Transplantation,Key Laboratory of Organ Transplantation,Chinese Academy of Medical Sciences,Wuhan,430030,China

出　　处：《Neuroscience Bulletin》2025年第1期61-76,共16页神经科学通报(英文版)

基　　金：supported by the National Natural Science Foundation of China(31670876 and 82171761).

摘　　要：IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis.However,their involvement in optic neuropathy due to trauma and glaucoma remains unclear.Here,we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina.Deletion of IL-33 or ST2 exacerbated retinal ganglion cell(RGC)loss,retinal thinning,and nerve fiber degeneration following optic nerve(ON)injury.This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33-/-mice.In vitro,rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors,thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants.Exogenous IL-33 treatment improved RGC survival in Il33-/-and WT mice after ON injury,but not in ST2-/-mice.Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.

关 键 词：KeywordsIL-33 ST2 Optic nerve injury-Retinal neurodegeneration ASTROCYTE NEUROPROTECTION 

分 类 号：R54[医药卫生—心血管疾病]