Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, and State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou, 325003, China.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.
Prog Retin Eye Res. 2019 Nov;73:100766. doi: 10.1016/j.preteyeres.2019.06.002. Epub 2019 Jun 23.
Dysfunction and loss of the retinal pigment epithelium (RPE) are hallmarks of retinal degenerative diseases in mammals. A critical transcription factor for RPE development and function is the microphthalmia-associated transcription factor MITF and its germline mutations are associated with clinically distinct disorders, including albinism, microphthalmia, retinal degeneration, and increased risk of developing melanoma. Many studies have revealed new insights into central roles of MITF in RPE cell physiology, including melanogenesis, regulation of trophic factor expression, cell proliferation, anti-oxidant functions, and the visual cycle. In this review, we discuss the complex functional roles of MITF in RPE development, homeostasis, and retinal degeneration and touch upon key questions and challenges in neuroprotective strategies for retinal degenerative disorders associated with deficiencies in MITF or its many target genes.
视网膜色素上皮 (RPE) 的功能障碍和丧失是哺乳动物视网膜退行性疾病的标志。小眼畸形相关转录因子 MITF 是 RPE 发育和功能的关键转录因子，其种系突变与临床上不同的疾病有关，包括白化病、小眼畸形、视网膜变性和黑色素瘤发病风险增加。许多研究揭示了 MITF 在 RPE 细胞生理学中的核心作用的新见解，包括黑色素生成、营养因子表达的调节、细胞增殖、抗氧化功能和视觉循环。在这篇综述中，我们讨论了 MITF 在 RPE 发育、稳态和视网膜变性中的复杂功能作用，并探讨了与 MITF 或其许多靶基因缺乏相关的视网膜退行性疾病的神经保护策略中的关键问题和挑战。
