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Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have...

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Autores principales: Lyu, Danni, Zhang, Lifang, Qin, Zhenwei, Ni, Shuang, Li, Jiayong, Lu, Bing, Hao, Shengjie, Tang, Qiaomei, Yin, Houfa, Chen, Zhijian, Yan, Yong-Bin, Ji, Junfeng, He, Jiliang, Nagy, Andras, Fu, Qiuli, Yao, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486789/
https://www.ncbi.nlm.nih.gov/pubmed/34599192
http://dx.doi.org/10.1038/s41536-021-00171-x
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author Lyu, Danni
Zhang, Lifang
Qin, Zhenwei
Ni, Shuang
Li, Jiayong
Lu, Bing
Hao, Shengjie
Tang, Qiaomei
Yin, Houfa
Chen, Zhijian
Yan, Yong-Bin
Ji, Junfeng
He, Jiliang
Nagy, Andras
Fu, Qiuli
Yao, Ke
author_facet Lyu, Danni
Zhang, Lifang
Qin, Zhenwei
Ni, Shuang
Li, Jiayong
Lu, Bing
Hao, Shengjie
Tang, Qiaomei
Yin, Houfa
Chen, Zhijian
Yan, Yong-Bin
Ji, Junfeng
He, Jiliang
Nagy, Andras
Fu, Qiuli
Yao, Ke
author_sort Lyu, Danni
collection PubMed
description Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients’ cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients’ cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.
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spelling pubmed-84867892021-10-07 Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells Lyu, Danni Zhang, Lifang Qin, Zhenwei Ni, Shuang Li, Jiayong Lu, Bing Hao, Shengjie Tang, Qiaomei Yin, Houfa Chen, Zhijian Yan, Yong-Bin Ji, Junfeng He, Jiliang Nagy, Andras Fu, Qiuli Yao, Ke NPJ Regen Med Article Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients’ cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients’ cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment. Nature Publishing Group UK 2021-10-01 /pmc/articles/PMC8486789/ /pubmed/34599192 http://dx.doi.org/10.1038/s41536-021-00171-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lyu, Danni
Zhang, Lifang
Qin, Zhenwei
Ni, Shuang
Li, Jiayong
Lu, Bing
Hao, Shengjie
Tang, Qiaomei
Yin, Houfa
Chen, Zhijian
Yan, Yong-Bin
Ji, Junfeng
He, Jiliang
Nagy, Andras
Fu, Qiuli
Yao, Ke
Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title_full Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title_fullStr Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title_full_unstemmed Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title_short Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
title_sort modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486789/
https://www.ncbi.nlm.nih.gov/pubmed/34599192
http://dx.doi.org/10.1038/s41536-021-00171-x
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