MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium
Oxidative damage is one of the major contributors to retinal degenerative diseases such as age-related macular degeneration (AMD), while RPE mediated antioxidant defense plays an important role in preventing retinopathies. However, the regulatory mechanisms of antioxidant signaling in RPE cells are...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720302718 |
| _version_ | 1818278217161637888 |
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| author | Shuxian Han Jianjun Chen Jiajia Hua Xiaojuan Hu Shuhui Jian Guoxiao Zheng Jing Wang Huirong Li Jinglei Yang J. Fielding Hejtmancik Jia Qu Xiaoyin Ma Ling Hou |
| author_facet | Shuxian Han Jianjun Chen Jiajia Hua Xiaojuan Hu Shuhui Jian Guoxiao Zheng Jing Wang Huirong Li Jinglei Yang J. Fielding Hejtmancik Jia Qu Xiaoyin Ma Ling Hou |
| author_sort | Shuxian Han |
| collection | DOAJ |
| description | Oxidative damage is one of the major contributors to retinal degenerative diseases such as age-related macular degeneration (AMD), while RPE mediated antioxidant defense plays an important role in preventing retinopathies. However, the regulatory mechanisms of antioxidant signaling in RPE cells are poorly understood. Here we show that transcription factor MITF regulates the antioxidant response in RPE cells, protecting the neural retina from oxidative damage. In the oxidative stress-induced retinal degeneration mouse model, retinal degeneration in Mitf+/- mice is significantly aggravated compared to WT mice. In contrast, overexpression of Mitf in Dct-Mitf transgenic mice and AAV mediated overexpression in RPE cells protect the neural retina against oxidative damage. Mechanistically, MITF both directly regulates the transcription of NRF2, a master regulator of antioxidant signaling, and promotes its nuclear translocation. Furthermore, specific overexpression of NRF2 in Mitf+/- RPE cells activates antioxidant signaling and partially protects the retina from oxidative damage. Taken together, our findings demonstrate the regulation of NRF2 by MITF in RPE cells and provide new insights into potential therapeutic approaches for prevention of oxidative damage diseases. |
| first_indexed | 2024-12-12T23:13:55Z |
| format | Article |
| id | doaj.art-710e7c556e6348e7b54b447cbde0b986 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-12T23:13:55Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-710e7c556e6348e7b54b447cbde0b9862022-12-22T00:08:31ZengElsevierRedox Biology2213-23172020-07-0134101537MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epitheliumShuxian Han0Jianjun Chen1Jiajia Hua2Xiaojuan Hu3Shuhui Jian4Guoxiao Zheng5Jing Wang6Huirong Li7Jinglei Yang8J. Fielding Hejtmancik9Jia Qu10Xiaoyin Ma11Ling Hou12Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, ChinaBirth defect group, Translation Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200081, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; Department of Ophthalmology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, ChinaLaboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, ChinaState Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, ChinaOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USAState Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China; Corresponding author.Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China; Corresponding author. Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China.Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, ChinaOxidative damage is one of the major contributors to retinal degenerative diseases such as age-related macular degeneration (AMD), while RPE mediated antioxidant defense plays an important role in preventing retinopathies. However, the regulatory mechanisms of antioxidant signaling in RPE cells are poorly understood. Here we show that transcription factor MITF regulates the antioxidant response in RPE cells, protecting the neural retina from oxidative damage. In the oxidative stress-induced retinal degeneration mouse model, retinal degeneration in Mitf+/- mice is significantly aggravated compared to WT mice. In contrast, overexpression of Mitf in Dct-Mitf transgenic mice and AAV mediated overexpression in RPE cells protect the neural retina against oxidative damage. Mechanistically, MITF both directly regulates the transcription of NRF2, a master regulator of antioxidant signaling, and promotes its nuclear translocation. Furthermore, specific overexpression of NRF2 in Mitf+/- RPE cells activates antioxidant signaling and partially protects the retina from oxidative damage. Taken together, our findings demonstrate the regulation of NRF2 by MITF in RPE cells and provide new insights into potential therapeutic approaches for prevention of oxidative damage diseases.http://www.sciencedirect.com/science/article/pii/S2213231720302718AntioxidantRetinal degenerationNRF2RPEMITF |
| spellingShingle | Shuxian Han Jianjun Chen Jiajia Hua Xiaojuan Hu Shuhui Jian Guoxiao Zheng Jing Wang Huirong Li Jinglei Yang J. Fielding Hejtmancik Jia Qu Xiaoyin Ma Ling Hou MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium Redox Biology Antioxidant Retinal degeneration NRF2 RPE MITF |
| title | MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium |
| title_full | MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium |
| title_fullStr | MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium |
| title_full_unstemmed | MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium |
| title_short | MITF protects against oxidative damage-induced retinal degeneration by regulating the NRF2 pathway in the retinal pigment epithelium |
| title_sort | mitf protects against oxidative damage induced retinal degeneration by regulating the nrf2 pathway in the retinal pigment epithelium |
| topic | Antioxidant Retinal degeneration NRF2 RPE MITF |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720302718 |
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