Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury  

作　　者：Yanan Dou Xiaowei Fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu Zhou Fei Xia Li Fei Fei 

机构地区：[1]Department of Neurosurgery,Xijing Hospital,Air Force Military Medical University,Xi’an,Shaanxi Province,China [2]Department of Ophthalmology,Xijing Hospital,Air Force Military Medical University,Xi’an,Shaanxi Province,China

出　　处：《Neural Regeneration Research》2024年第7期1608-1617,共10页中国神经再生研究（英文版）

基　　金：supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072;Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。

摘　　要：Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关 键 词：CASPASE-8 Homer1a INTERLEUKIN-18 INTERLEUKIN-1Β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 RETINA 

分 类 号：R774.1[医药卫生—眼科] R-332[医药卫生—临床医学]