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D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration
Accumulated oxidative damage may lead to irreversible retinal pigmented epithelium (RPE) cell death, which is considered to be the primary cause of dry age-related macular degeneration (AMD), leading to blindness in the elderly. However, an effective therapy for this disease is lacking. Here, we des...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054264/ https://www.ncbi.nlm.nih.gov/pubmed/32296021 http://dx.doi.org/10.1038/s41392-020-0122-1 |
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author | Wang, Bowen Wang, Li Gu, Sijie Yu, Yankun Huang, Huaxing Mo, Kunlun Xu, He Zeng, Fanzhu Xiao, Yichen Peng, Lulu Liu, Chunqiao Cao, Nan Liu, Yizhi Yuan, Jin Ouyang, Hong |
author_facet | Wang, Bowen Wang, Li Gu, Sijie Yu, Yankun Huang, Huaxing Mo, Kunlun Xu, He Zeng, Fanzhu Xiao, Yichen Peng, Lulu Liu, Chunqiao Cao, Nan Liu, Yizhi Yuan, Jin Ouyang, Hong |
author_sort | Wang, Bowen |
collection | PubMed |
description | Accumulated oxidative damage may lead to irreversible retinal pigmented epithelium (RPE) cell death, which is considered to be the primary cause of dry age-related macular degeneration (AMD), leading to blindness in the elderly. However, an effective therapy for this disease is lacking. Here, we described a robust high-content screening procedure with a library of 814 protective compounds and found that D609 strongly protected RPE cells from sodium iodate (SI)-induced oxidative cell death and prolonged their healthy survival. D609 effectively attenuated excessive reactive oxygen species (ROS) and prevented severe mitochondrial loss due to oxidative stress in the RPE cells. Surprisingly, the potent antioxidative effects of D609 were not achieved through its own reducibility but were primarily dependent on its ability to increase the expression of metallothionein. The injection of this small water-soluble molecule also showed an explicit protective effect of the RPE layer in an SI-induced AMD mouse model. These findings suggested that D609 could serve as a novel antioxidative protector of RPE cells both in vitro and in vivo and unveiled a novel antioxidative mechanism of D609, which may ultimately have clinical applications for the treatment of AMD. |
format | Online Article Text |
id | pubmed-7054264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70542642020-03-19 D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration Wang, Bowen Wang, Li Gu, Sijie Yu, Yankun Huang, Huaxing Mo, Kunlun Xu, He Zeng, Fanzhu Xiao, Yichen Peng, Lulu Liu, Chunqiao Cao, Nan Liu, Yizhi Yuan, Jin Ouyang, Hong Signal Transduct Target Ther Article Accumulated oxidative damage may lead to irreversible retinal pigmented epithelium (RPE) cell death, which is considered to be the primary cause of dry age-related macular degeneration (AMD), leading to blindness in the elderly. However, an effective therapy for this disease is lacking. Here, we described a robust high-content screening procedure with a library of 814 protective compounds and found that D609 strongly protected RPE cells from sodium iodate (SI)-induced oxidative cell death and prolonged their healthy survival. D609 effectively attenuated excessive reactive oxygen species (ROS) and prevented severe mitochondrial loss due to oxidative stress in the RPE cells. Surprisingly, the potent antioxidative effects of D609 were not achieved through its own reducibility but were primarily dependent on its ability to increase the expression of metallothionein. The injection of this small water-soluble molecule also showed an explicit protective effect of the RPE layer in an SI-induced AMD mouse model. These findings suggested that D609 could serve as a novel antioxidative protector of RPE cells both in vitro and in vivo and unveiled a novel antioxidative mechanism of D609, which may ultimately have clinical applications for the treatment of AMD. Nature Publishing Group UK 2020-03-04 /pmc/articles/PMC7054264/ /pubmed/32296021 http://dx.doi.org/10.1038/s41392-020-0122-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Bowen Wang, Li Gu, Sijie Yu, Yankun Huang, Huaxing Mo, Kunlun Xu, He Zeng, Fanzhu Xiao, Yichen Peng, Lulu Liu, Chunqiao Cao, Nan Liu, Yizhi Yuan, Jin Ouyang, Hong D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title | D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title_full | D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title_fullStr | D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title_full_unstemmed | D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title_short | D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
title_sort | d609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054264/ https://www.ncbi.nlm.nih.gov/pubmed/32296021 http://dx.doi.org/10.1038/s41392-020-0122-1 |
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