Retinal safety and toxicity study of artesunate in vitro and in vivo
Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Advances in Ophthalmology Practice and Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667376222000762 |
| _version_ | 1827951703334322176 |
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| author | Bing-Wen Lu Yu-Xiang Liang Jin-Feng Liu Zhong-Qing Sun Kwok-Fai So Kin Chiu |
| author_facet | Bing-Wen Lu Yu-Xiang Liang Jin-Feng Liu Zhong-Qing Sun Kwok-Fai So Kin Chiu |
| author_sort | Bing-Wen Lu |
| collection | DOAJ |
| description | Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5μM was safe for IMG cells in vitro. Both 2.5 and 5 μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 μM significantly decreased TNF-α gene expression while ART of 100 μM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 μM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders. |
| first_indexed | 2024-04-09T13:45:40Z |
| format | Article |
| id | doaj.art-299418bac2ee4a47bed0b4425d3db594 |
| institution | Directory Open Access Journal |
| issn | 2667-3762 |
| language | English |
| last_indexed | 2024-04-09T13:45:40Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Ophthalmology Practice and Research |
| spelling | doaj.art-299418bac2ee4a47bed0b4425d3db5942023-05-09T04:05:29ZengElsevierAdvances in Ophthalmology Practice and Research2667-37622023-05-01324754Retinal safety and toxicity study of artesunate in vitro and in vivoBing-Wen Lu0Yu-Xiang Liang1Jin-Feng Liu2Zhong-Qing Sun3Kwok-Fai So4Kin Chiu5Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Department of Psychology, Faculty of Social Sciences, The University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Department of Psychology, Faculty of Social Sciences, The University of Hong Kong, Hong Kong, China; Guangdong-Hongkong-Macau (GHM) Institute of CNS Regeneration, Ministry of Education, CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaDepartment of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Department of Psychology, Faculty of Social Sciences, The University of Hong Kong, Hong Kong, China; Corresponding author. State Key Laboratory of Brain and Cognitive Sciences, Department of Psychology, The University of Hong Kong, 5 Sassoon Road, Pokfulam, Hong Kong, China.Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5μM was safe for IMG cells in vitro. Both 2.5 and 5 μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 μM significantly decreased TNF-α gene expression while ART of 100 μM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 μM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.http://www.sciencedirect.com/science/article/pii/S2667376222000762ArtesunateSafetyRetinaMicroglia |
| spellingShingle | Bing-Wen Lu Yu-Xiang Liang Jin-Feng Liu Zhong-Qing Sun Kwok-Fai So Kin Chiu Retinal safety and toxicity study of artesunate in vitro and in vivo Advances in Ophthalmology Practice and Research Artesunate Safety Retina Microglia |
| title | Retinal safety and toxicity study of artesunate in vitro and in vivo |
| title_full | Retinal safety and toxicity study of artesunate in vitro and in vivo |
| title_fullStr | Retinal safety and toxicity study of artesunate in vitro and in vivo |
| title_full_unstemmed | Retinal safety and toxicity study of artesunate in vitro and in vivo |
| title_short | Retinal safety and toxicity study of artesunate in vitro and in vivo |
| title_sort | retinal safety and toxicity study of artesunate in vitro and in vivo |
| topic | Artesunate Safety Retina Microglia |
| url | http://www.sciencedirect.com/science/article/pii/S2667376222000762 |
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