Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome
Abstract Quantum dots (QDs) are widely used, but their health impact on the visual system is little known. This study aims to elucidate the effects and mechanisms of typical metallic QDs on retinas using zebrafish. Comprehensive histology, imaging, and bulk RNA sequencing reveal that InP/ZnS QDs cau...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406343 |
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| author | Naying Zheng Tingting Liao Chuchu Zhang Zheyang Zhang Sen Yan Xiaohan Xi Fengkai Ruan Chunyan Yang Qingliang Zhao Wenbo Deng Jialiang Huang Zi‐Tao Huang Zhi‐Feng Chen Xiang Wang Qingming Qu Zhenghong Zuo Chengyong He |
| author_facet | Naying Zheng Tingting Liao Chuchu Zhang Zheyang Zhang Sen Yan Xiaohan Xi Fengkai Ruan Chunyan Yang Qingliang Zhao Wenbo Deng Jialiang Huang Zi‐Tao Huang Zhi‐Feng Chen Xiang Wang Qingming Qu Zhenghong Zuo Chengyong He |
| author_sort | Naying Zheng |
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| description | Abstract Quantum dots (QDs) are widely used, but their health impact on the visual system is little known. This study aims to elucidate the effects and mechanisms of typical metallic QDs on retinas using zebrafish. Comprehensive histology, imaging, and bulk RNA sequencing reveal that InP/ZnS QDs cause retinal degeneration. Furthermore, single‐cell RNA‐seq reveals a reduction in the number of retinal pigment epithelial cells (RPE) and short‐wave cone UV photoreceptor cells (PR(UV)), accompanied by an increase in middle‐ and long‐wave cone red, green, and blue photoreceptor cells [PR(RGB)]. Mechanistically, after endocytosis by RPE, InP/ZnS QDs inhibit the expression of splicing factor prpf8, resulting in gpx4b mRNA unsplicing, which finally decrease glutathione and induce ferroptosis and mitophagy. The decrease of RPE fails to engulf the damaged outer segments of PR, possibly promoting the differentiation of PR(UV) to PR(RGB). Knockout prpf8 or gpx4b with CRISPR/Cas9 system, the retinal damage is also observed. Whereas, overexpression of prpf8 or gpx4b, or supplement of glutathione can rescue the retinal degenerative damage caused by InP/ZnS QDs. In conclusion, this study illustrates the potential health risks of InP/ZnS QDs on eye development and provides valuable insights into the underlying mechanisms of InP/ZnS QDs‐caused retinal degeneration. |
| format | Article |
| id | doaj-art-e0f9742b1f1d45bca589df1e1f1e5cdf |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e0f9742b1f1d45bca589df1e1f1e5cdf2024-12-11T16:00:49ZengWileyAdvanced Science2198-38442024-12-011146n/an/a10.1002/advs.202406343Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting SpliceosomeNaying Zheng0Tingting Liao1Chuchu Zhang2Zheyang Zhang3Sen Yan4Xiaohan Xi5Fengkai Ruan6Chunyan Yang7Qingliang Zhao8Wenbo Deng9Jialiang Huang10Zi‐Tao Huang11Zhi‐Feng Chen12Xiang Wang13Qingming Qu14Zhenghong Zuo15Chengyong He16Department of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Chemistry State Key Laboratory of Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials (i‐ChEM) Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 ChinaDepartment of Chemistry State Key Laboratory of Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials (i‐ChEM) Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaState Key Laboratory of Vaccines for Infectious Diseases Center for Molecular Imaging and Translational Medicine Xiang An Biomedicine Laboratory School of Public Health Xiamen University Xiamen Fujian 361005 ChinaKey Laboratory of Reproductive Health Research Fujian Province University School of Medicine Xiamen University Xiamen Fujian 361005 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaGuangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangdong‐Hong Kong‐Macao Joint Laboratory for Contaminants Exposure and Health School of Environmental Science and Engineering Guangdong University of Technology Guangzhou 510006 ChinaGuangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangdong‐Hong Kong‐Macao Joint Laboratory for Contaminants Exposure and Health School of Environmental Science and Engineering Guangdong University of Technology Guangzhou 510006 ChinaDepartment of Chemistry State Key Laboratory of Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials (i‐ChEM) Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaDepartment of Ophthalmology in Xiang'an Hospital of Xiamen University State Key Laboratory of Cellular Stress Biology School of Life Sciences Faculty of Medicine and Life Sciences Xiamen University Xiamen Fujian 361102 ChinaAbstract Quantum dots (QDs) are widely used, but their health impact on the visual system is little known. This study aims to elucidate the effects and mechanisms of typical metallic QDs on retinas using zebrafish. Comprehensive histology, imaging, and bulk RNA sequencing reveal that InP/ZnS QDs cause retinal degeneration. Furthermore, single‐cell RNA‐seq reveals a reduction in the number of retinal pigment epithelial cells (RPE) and short‐wave cone UV photoreceptor cells (PR(UV)), accompanied by an increase in middle‐ and long‐wave cone red, green, and blue photoreceptor cells [PR(RGB)]. Mechanistically, after endocytosis by RPE, InP/ZnS QDs inhibit the expression of splicing factor prpf8, resulting in gpx4b mRNA unsplicing, which finally decrease glutathione and induce ferroptosis and mitophagy. The decrease of RPE fails to engulf the damaged outer segments of PR, possibly promoting the differentiation of PR(UV) to PR(RGB). Knockout prpf8 or gpx4b with CRISPR/Cas9 system, the retinal damage is also observed. Whereas, overexpression of prpf8 or gpx4b, or supplement of glutathione can rescue the retinal degenerative damage caused by InP/ZnS QDs. In conclusion, this study illustrates the potential health risks of InP/ZnS QDs on eye development and provides valuable insights into the underlying mechanisms of InP/ZnS QDs‐caused retinal degeneration.https://doi.org/10.1002/advs.202406343FerroptosisQuantum dotsRetinal degenerationSingle‐cell RNA sequencingSpliceosome |
| spellingShingle | Naying Zheng Tingting Liao Chuchu Zhang Zheyang Zhang Sen Yan Xiaohan Xi Fengkai Ruan Chunyan Yang Qingliang Zhao Wenbo Deng Jialiang Huang Zi‐Tao Huang Zhi‐Feng Chen Xiang Wang Qingming Qu Zhenghong Zuo Chengyong He Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome Advanced Science Ferroptosis Quantum dots Retinal degeneration Single‐cell RNA sequencing Spliceosome |
| title | Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome |
| title_full | Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome |
| title_fullStr | Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome |
| title_full_unstemmed | Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome |
| title_short | Quantum Dots‐caused Retinal Degeneration in Zebrafish Regulated by Ferroptosis and Mitophagy in Retinal Pigment Epithelial Cells through Inhibiting Spliceosome |
| title_sort | quantum dots caused retinal degeneration in zebrafish regulated by ferroptosis and mitophagy in retinal pigment epithelial cells through inhibiting spliceosome |
| topic | Ferroptosis Quantum dots Retinal degeneration Single‐cell RNA sequencing Spliceosome |
| url | https://doi.org/10.1002/advs.202406343 |
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