期刊
REDOX BIOLOGY
卷 34, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2020.101537
关键词
Antioxidant; Retinal degeneration; NRF2; RPE; MITF
资金
- National Natural Science Foundation of China [81870664, 81770946, 81570892, 81600748, 81800838]
- Research Grant of Wenzhou Medical University Eye Hospital [KYQD151211, YNZD201605]
- Project of State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University [437201804G]
- NATIONAL EYE INSTITUTE [ZIAEY000272] Funding Source: NIH RePORTER
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 re-tinopathies. 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 signi ficantly 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, speci fic 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.
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