Roles of Optineurin and Extracellular Vesicles in Glaucomatous Retinal Cell Loss  

作　　者：Chao-ye DUAN Wan-lin FAN Fei CHEN 

机构地区：[1]Department of Ophthalmology,Renmin Hospital of Wuhan University,Wuhan,430060,China [2]Department of Ophthalmology,University of Cologne,Faculty of Medicine and University Hospital Cologne,Cologne,50937,Germany [3]Department of Ophthalmology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China

出　　处：《Current Medical Science》2023年第2期367-375,共9页当代医学科学（英文）

基　　金：supported by grants from the Wuhan Science and Technology Bureau(No.02.07.17040008.05);the Fundamental Research Funds for the Central Universities(2042020kf0099);the Opening Foundation of Hubei Key Laboratory(No.2021KFY054).

摘　　要：Objective To explore the role of extracellular vesicles(EVs)in the pathogenesis of glaucoma caused by E50K mutation.Methods A photoreceptor cell line,RGC-5,was transfected with empty plasmids and plasmids expressing wild-type(WT)optineurin(OPTN)or E50K OPTN to investigate the effects of OPTN glaucoma as well as to identify the role of EVs in glaucoma pathology.The RGC-5 cells were also stimulated with glutamate,and their viability was evaluated using flow cytometry or CCK-8 assay.EVs were extracted,labeled with PKH-26,and added into the medium for normal RGC-5 culture,and the status of the cells was observed thereafter.Results WT OPTN overexpression,E50K OPTN,and glutamate stimulation induced apoptosis of RGC-5 cells.However,when glutamate stimulation was used as an add-on treatment,the degree of apoptosis in WT OPTN-overexpressing RGC-5 cells was significantly lower than that in E50K OPTN-expressing and normal RGC-5 cells.The viability of normal RGC-5 cells was reduced when co-cultured with WT OPTN-overexpressing RGC-5 or E50K OPTN-overexpressing RGC-5.EVs released by the latter two transfected lines similarly reduced normal RGC-5 survival.Conclusion Our results indicate that WT OPTN overexpression may lead to photoreceptor apoptosis.However,overexpression also confers a degree of protection against high concentrations of extracellular glutamate.Additionally,EVs released by transfected RGC-5 cells may regulate the cell state.These findings may improve our understanding of the mechanisms of cell-cell interactions in pathological conditions,providing a basis for the use of EVs as novel targets for early diagnosis and treatment of glaucoma.

关 键 词：E50K mutation extracellular vesicles GLAUCOMA OPTINEURIN RGC-5 photoreceptor cell line 

分 类 号：R775[医药卫生—眼科]