iPSC-based model of Vogt-Koyanagi-Harada disease for phenotype recapitulation and drug screening

作者全名："Li, Wanqian; Tan, Jun; He, Siyuan; Yue, Yingying; Liu, Huan; Li, Ruonan; Wang, Xiaotang; Wang, Guoqing; Fan, Wei; Zhao, Chenyang; Zhou, Qian; Yang, Peizeng; Hou, Shengping"

作者地址："[Li, Wanqian; Tan, Jun; He, Siyuan; Yue, Yingying; Liu, Huan; Li, Ruonan; Wang, Xiaotang; Wang, Guoqing; Fan, Wei; Zhao, Chenyang; Zhou, Qian; Yang, Peizeng; Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Wanqian; Tan, Jun; He, Siyuan; Yue, Yingying; Liu, Huan; Li, Ruonan; Wang, Xiaotang; Wang, Guoqing; Fan, Wei; Zhao, Chenyang; Zhou, Qian; Yang, Peizeng; Hou, Shengping] Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Li, Wanqian; Tan, Jun; He, Siyuan; Yue, Yingying; Liu, Huan; Li, Ruonan; Wang, Xiaotang; Wang, Guoqing; Fan, Wei; Zhao, Chenyang; Zhou, Qian; Yang, Peizeng; Hou, Shengping] Chongqing Eye Inst, Chongqing, Peoples R China; [Li, Wanqian; Tan, Jun; He, Siyuan; Yue, Yingying; Liu, Huan; Li, Ruonan; Wang, Xiaotang; Wang, Guoqing; Fan, Wei; Zhao, Chenyang; Zhou, Qian; Yang, Peizeng; Hou, Shengping] Chongqing Branch Municipal Div Natl Clin Res Ctr O, Chongqing, Peoples R China"

通信作者："Yang, PZ; Hou, SP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000906251900001

JCR分区：Q2

影响因子：4.5

年份：2023

卷号：246

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Vogt-Koyanagi-Harada (VKH) disease; Induced pluripotent stem cells (iPSCs); Retinal pigment epithelium (RPE); Drug screening; Early growth response gene 2 (EGR2)

摘要："Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease."

基金机构："National Natural Science Foundation Project of China [81873678, 82070951, 82271078]; Innovative Research Group Project of Chongqing Education Commission [CXQT19015]; Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0120]; Innovation Supporting Plan of Overseas Study of Chongqing [cx2018010]; Chongqing Education Commission [KJQN202000406]; National Key Clinical Specialties Construction Program of China, Chongqing Branch of National Clinical Research Center for Ocular Diseases; Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [w0047]"

基金资助正文："This work was supported by National Natural Science Foundation Project of China (81873678, 82070951, 82271078) ; the Innovative Research Group Project of Chongqing Education Commission (CXQT19015) ; the Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0120) ; the Innovation Supporting Plan of Overseas Study of Chongqing (cx2018010) ; the Chongqing Education Commission (KJQN202000406) ; the National Key Clinical Specialties Construction Program of China, Chongqing Branch of National Clinical Research Center for Ocular Diseases; the Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003) and Program for Youth Innova- tion in Future Medicine, Chongqing Medical University (w0047) ."