Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells
AIM: To explore the changes in early retinal development after the occurrence of ischemia. METHODS: Human retinal organoids (hROs) of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion (OGD/R) to simulate the retinal ischemia. All hROs were maintained normally until day 60...
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Press of International Journal of Ophthalmology (IJO PRESS)
2025-08-01
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| Series: | International Journal of Ophthalmology |
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| Online Access: | http://ies.ijo.cn/en_publish/2025/8/20250803.pdf |
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| author | Yu-Han Yan Hong-Yu Li Li-Xiong Gao Wen Li Ling-Ping Zhao Quan Zeng Yu Luo Tian-Tian Cui Ru-Ge Zang Zi Ye Jia-Fei Xi Wen Yue Zhao-Hui Li |
| author_facet | Yu-Han Yan Hong-Yu Li Li-Xiong Gao Wen Li Ling-Ping Zhao Quan Zeng Yu Luo Tian-Tian Cui Ru-Ge Zang Zi Ye Jia-Fei Xi Wen Yue Zhao-Hui Li |
| author_sort | Yu-Han Yan |
| collection | DOAJ |
| description | AIM: To explore the changes in early retinal development after the occurrence of ischemia. METHODS: Human retinal organoids (hROs) of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion (OGD/R) to simulate the retinal ischemia. All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development. Paraffin section staining was used for detecting changes in organoid structure and cell number. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analyses were used to observe the change in the expression of retinal cell markers. RESULTS: In hROs, OGD/R induced the decrease of proliferating cells, inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells (P<0.05). Under OGD/R condition, the progenitor cell layer and ganglion cell layer of hROs lost normal structure, and the number of neural stem cells (SOX2+), retinal progenitor cells (CHX10+) and retinal ganglion cells (TUJ1+/BRN3+/ATOH7+) decreased (P<0.05). The expression of corresponding retinal cell markers also decreased (P<0.05). Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18. Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60, with no recovery in proliferating cell nuclear antigen (PCNA) protein expression. RT-qPCR showed persistently low Ki67 transcription levels (P<0.001), while other retinal cell markers recovered or exceeded normal levels, indicating a limited self-repair happened in the development of hROs. In contrast, day 30-treated organoids exhibited normal structure and marker expression by day 60, with transcription levels of retinal cell markers returning to normal (P>0.05), demonstrating complete recovery from OGD/R damage. CONCLUSION: Retinal ischemia damage the retinal development in the short-term. After the restoration of retinal blood supply, the retinal ischemic damage can be recovered during subsequent development. However, retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility. The earlier ischemic injury occurs, the more difficult it is to repair retinal cell and structure damage. |
| format | Article |
| id | doaj-art-33c683aa0b314dc39a92d7fda76d87b3 |
| institution | DOAJ |
| issn | 2222-3959 2227-4898 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj-art-33c683aa0b314dc39a92d7fda76d87b32025-08-20T03:12:38ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982025-08-011881433144910.18240/ijo.2025.08.0320250803Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cellsYu-Han Yan0Hong-Yu Li1Li-Xiong Gao2Wen Li3Ling-Ping Zhao4Quan Zeng5Yu Luo6Tian-Tian Cui7Ru-Ge Zang8Zi Ye9Jia-Fei Xi10Wen Yue11Zhao-Hui Li12Zhao-Hui Li. Senior Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, China. zhaohuili202104@163.com; Wen Yue. Beijing Institute of Radiation Medicine, Beijing 100850, China. yuewen@bmi.ac.cnBeijing Institute of Radiation Medicine, Beijing 100850, ChinaSenior Department of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, ChinaMedical School of Chinese PLA, Beijing 100853, China; Senior Department of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaMedical School of Chinese PLA, Beijing 100853, China; Senior Department of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaMedical School of Chinese PLA, Beijing 100853, China; Senior Department of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaMedical School of Chinese PLA, Beijing 100853, China; Senior Department of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, ChinaAIM: To explore the changes in early retinal development after the occurrence of ischemia. METHODS: Human retinal organoids (hROs) of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion (OGD/R) to simulate the retinal ischemia. All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development. Paraffin section staining was used for detecting changes in organoid structure and cell number. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analyses were used to observe the change in the expression of retinal cell markers. RESULTS: In hROs, OGD/R induced the decrease of proliferating cells, inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells (P<0.05). Under OGD/R condition, the progenitor cell layer and ganglion cell layer of hROs lost normal structure, and the number of neural stem cells (SOX2+), retinal progenitor cells (CHX10+) and retinal ganglion cells (TUJ1+/BRN3+/ATOH7+) decreased (P<0.05). The expression of corresponding retinal cell markers also decreased (P<0.05). Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18. Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60, with no recovery in proliferating cell nuclear antigen (PCNA) protein expression. RT-qPCR showed persistently low Ki67 transcription levels (P<0.001), while other retinal cell markers recovered or exceeded normal levels, indicating a limited self-repair happened in the development of hROs. In contrast, day 30-treated organoids exhibited normal structure and marker expression by day 60, with transcription levels of retinal cell markers returning to normal (P>0.05), demonstrating complete recovery from OGD/R damage. CONCLUSION: Retinal ischemia damage the retinal development in the short-term. After the restoration of retinal blood supply, the retinal ischemic damage can be recovered during subsequent development. However, retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility. The earlier ischemic injury occurs, the more difficult it is to repair retinal cell and structure damage.http://ies.ijo.cn/en_publish/2025/8/20250803.pdfretinal diseasesfetal ischemiaoxygen-glucose deprivation and reperfusionhuman retinal organoidsretinal ganglion cells |
| spellingShingle | Yu-Han Yan Hong-Yu Li Li-Xiong Gao Wen Li Ling-Ping Zhao Quan Zeng Yu Luo Tian-Tian Cui Ru-Ge Zang Zi Ye Jia-Fei Xi Wen Yue Zhao-Hui Li Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells International Journal of Ophthalmology retinal diseases fetal ischemia oxygen-glucose deprivation and reperfusion human retinal organoids retinal ganglion cells |
| title | Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| title_full | Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| title_fullStr | Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| title_full_unstemmed | Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| title_short | Damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| title_sort | damaging effect of ischemia on the development of retinal organoids derived from human embryonic stem cells |
| topic | retinal diseases fetal ischemia oxygen-glucose deprivation and reperfusion human retinal organoids retinal ganglion cells |
| url | http://ies.ijo.cn/en_publish/2025/8/20250803.pdf |
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