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

Abstract 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 screen...

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Autores principales:	Danni Lyu, Lifang Zhang, Zhenwei Qin, Shuang Ni, Jiayong Li, Bing Lu, Shengjie Hao, Qiaomei Tang, Houfa Yin, Zhijian Chen, Yong-Bin Yan, Junfeng Ji, Jiliang He, Andras Nagy, Qiuli Fu, Ke Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/c9e3bb02cb784ed9aaa86a0a93fa30f6
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spelling	oai:doaj.org-article:c9e3bb02cb784ed9aaa86a0a93fa30f62021-12-02T17:17:42ZModeling congenital cataract in vitro using patient-specific induced pluripotent stem cells10.1038/s41536-021-00171-x2057-3995https://doaj.org/article/c9e3bb02cb784ed9aaa86a0a93fa30f62021-10-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00171-xhttps://doaj.org/toc/2057-3995Abstract 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.Danni LyuLifang ZhangZhenwei QinShuang NiJiayong LiBing LuShengjie HaoQiaomei TangHoufa YinZhijian ChenYong-Bin YanJunfeng JiJiliang HeAndras NagyQiuli FuKe YaoNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Danni Lyu Lifang Zhang Zhenwei Qin Shuang Ni Jiayong Li Bing Lu Shengjie Hao Qiaomei Tang Houfa Yin Zhijian Chen Yong-Bin Yan Junfeng Ji Jiliang He Andras Nagy Qiuli Fu Ke Yao Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
description	Abstract 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.
format	article
author	Danni Lyu Lifang Zhang Zhenwei Qin Shuang Ni Jiayong Li Bing Lu Shengjie Hao Qiaomei Tang Houfa Yin Zhijian Chen Yong-Bin Yan Junfeng Ji Jiliang He Andras Nagy Qiuli Fu Ke Yao
author_facet	Danni Lyu Lifang Zhang Zhenwei Qin Shuang Ni Jiayong Li Bing Lu Shengjie Hao Qiaomei Tang Houfa Yin Zhijian Chen Yong-Bin Yan Junfeng Ji Jiliang He Andras Nagy Qiuli Fu Ke Yao
author_sort	Danni Lyu
title	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_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_sort	modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c9e3bb02cb784ed9aaa86a0a93fa30f6
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_version_	1718381169021550592

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

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