Labratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China.
Labratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, China; State Key Laboratory of Ophthalmology, Optometry and Vision Science and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou, 325003, China.
Exp Eye Res. 2018 May;170:138-147. doi: 10.1016/j.exer.2018.02.023. Epub 2018 Feb 24.
There is increasing evidence that the mechanisms protecting the retinal pigment epithelium (RPE) against oxidative stress are important for preventing retinal degenerative diseases. Little, however, is known about these mechanisms. Here we show that MITF, a transcription factor responsible for RPE development and function, regulates redox signaling by acting through PGC1α, a master regulator of mitochondrial biogenesis. Mitf deficiency in mice leads to significantly higher levels of reactive oxygen species (ROS) in both RPE and retina, suggesting that Mitf dysfunction might lead to oxidative damage in the RPE and, by extension, in the retina. Furthermore, overexpression of MITF in the human RPE cell line ARPE-19 indicates that MITF up-regulates antioxidant gene expression and mitochondrial biogenesis by regulating PGC1α and protects cells against oxidative stress. Our findings provide new insights into understanding the redox function of MITF in RPE cells and its potential contribution to prevention of RPE-associated retinal degenerations.
越来越多的证据表明，保护视网膜色素上皮（RPE）免受氧化应激的机制对于预防视网膜退行性疾病很重要。然而，人们对这些机制知之甚少。在这里，我们发现，MITF 是一种负责 RPE 发育和功能的转录因子，它通过 PGC1α 调节氧化还原信号，PGC1α 是线粒体生物发生的主要调节因子。小鼠的 Mitf 缺失会导致 RPE 和视网膜中活性氧（ROS）的水平显著升高，这表明 Mitf 功能障碍可能导致 RPE 中的氧化损伤，并因此导致视网膜损伤。此外，在人 RPE 细胞系 ARPE-19 中过表达 MITF 表明，MITF 通过调节 PGC1α 而上调抗氧化基因表达和线粒体生物发生，并保护细胞免受氧化应激。我们的研究结果为理解 MITF 在 RPE 细胞中的氧化还原功能及其在预防与 RPE 相关的视网膜变性中的潜在作用提供了新的见解。
