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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-10-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-021-00171-x |
| _version_ | 1818846073836273664 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T05:39:46Z |
| format | Article |
| id | doaj.art-c9e3bb02cb784ed9aaa86a0a93fa30f6 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-12-19T05:39:46Z |
| publishDate | 2021-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-c9e3bb02cb784ed9aaa86a0a93fa30f62022-12-21T20:34:03ZengNature Portfolionpj Regenerative Medicine2057-39952021-10-016111410.1038/s41536-021-00171-xModeling congenital cataract in vitro using patient-specific induced pluripotent stem cellsDanni Lyu0Lifang Zhang1Zhenwei Qin2Shuang Ni3Jiayong Li4Bing Lu5Shengjie Hao6Qiaomei Tang7Houfa Yin8Zhijian Chen9Yong-Bin Yan10Junfeng Ji11Jiliang He12Andras Nagy13Qiuli Fu14Ke Yao15Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyDepartment of Environmental and Occupational Health, Zhejiang Provincial Center for Disease Control and PreventionState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua UniversityCenter of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative MedicineInstitute of Environmental Medicine, School of Medicine, Zhejiang UniversityLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Institute of Medical Science, University of TorontoEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyEye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of OphthalmologyAbstract 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.https://doi.org/10.1038/s41536-021-00171-x |
| spellingShingle | 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 npj Regenerative Medicine |
| 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 |
| url | https://doi.org/10.1038/s41536-021-00171-x |
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