Effects of paclitaxel on Müller cells in retina
AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups:...
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Press of International Journal of Ophthalmology (IJO PRESS)
2023-11-01
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Series: | Guoji Yanke Zazhi |
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Online Access: | http://ies.ijo.cn/cn_publish/2023/11/202311002.pdf |
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author | Yi-Xuan Xi Ya-Ting Ye Guo-Rui Dou Tian-Fang Chang Ya-Li Niu Zi-Yi Zhou Zhao-Jie Chu |
author_facet | Yi-Xuan Xi Ya-Ting Ye Guo-Rui Dou Tian-Fang Chang Ya-Li Niu Zi-Yi Zhou Zhao-Jie Chu |
author_sort | Yi-Xuan Xi |
collection | DOAJ |
description | AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P<0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P<0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina. |
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id | doaj.art-54b9bc7e9d684a05aef6c59a4feefab4 |
institution | Directory Open Access Journal |
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language | English |
last_indexed | 2024-03-11T16:32:08Z |
publishDate | 2023-11-01 |
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series | Guoji Yanke Zazhi |
spelling | doaj.art-54b9bc7e9d684a05aef6c59a4feefab42023-10-24T02:34:26ZengPress of International Journal of Ophthalmology (IJO PRESS)Guoji Yanke Zazhi1672-51232023-11-0123111775178010.3980/j.issn.1672-5123.2023.11.02202311002Effects of paclitaxel on Müller cells in retinaYi-Xuan Xi0Ya-Ting Ye1Guo-Rui Dou2Tian-Fang Chang3Ya-Li Niu4Zi-Yi Zhou5Zhao-Jie Chu6The College of Life Sciences, Northwest University, Xi'an 710000, Shaanxi Province, China; The First Affiliated Hospital of Northwest University;Xian No.1 Hospital, Xi'an 710002, Shaanxi Province, ChinaThe College of Life Sciences, Northwest University, Xi'an 710000, Shaanxi Province, China; The First Affiliated Hospital of Northwest University;Xian No.1 Hospital, Xi'an 710002, Shaanxi Province, China; Department of Ophthalmology, the First Affiliated Hospital of the Air Force Medical University, Xi'an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, the First Affiliated Hospital of the Air Force Medical University, Xi'an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, the First Affiliated Hospital of the Air Force Medical University, Xi'an 710032, Shaanxi Province, ChinaThe College of Life Sciences, Northwest University, Xi'an 710000, Shaanxi Province, China; Department of Ophthalmology, the First Affiliated Hospital of the Air Force Medical University, Xi'an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, the First Affiliated Hospital of the Air Force Medical University, Xi'an 710032, Shaanxi Province, ChinaThe First Affiliated Hospital of Northwest University;Xian No.1 Hospital, Xi'an 710002, Shaanxi Province, ChinaAIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P<0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P<0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina.http://ies.ijo.cn/cn_publish/2023/11/202311002.pdfpaclitaxelmüller cellsapoptosisproliferation |
spellingShingle | Yi-Xuan Xi Ya-Ting Ye Guo-Rui Dou Tian-Fang Chang Ya-Li Niu Zi-Yi Zhou Zhao-Jie Chu Effects of paclitaxel on Müller cells in retina Guoji Yanke Zazhi paclitaxel müller cells apoptosis proliferation |
title | Effects of paclitaxel on Müller cells in retina |
title_full | Effects of paclitaxel on Müller cells in retina |
title_fullStr | Effects of paclitaxel on Müller cells in retina |
title_full_unstemmed | Effects of paclitaxel on Müller cells in retina |
title_short | Effects of paclitaxel on Müller cells in retina |
title_sort | effects of paclitaxel on muller cells in retina |
topic | paclitaxel müller cells apoptosis proliferation |
url | http://ies.ijo.cn/cn_publish/2023/11/202311002.pdf |
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