Wen Bin, Li Shuang, Li Huirong, Chen Yu, Ma Xiaoyin, Wang Jing, Lu Fan, Qu Jia, Hou Ling
Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, 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.
Sci Rep. 2016 Feb 15;6:21208. doi: 10.1038/srep21208.
Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes, Rlbp1 which encodes retinaldehyde binding protein-1 (RLBP1), and Rdh5, which encodes retinol dehydrogenase-5 (RDH5). First, we found that Rlbp1 and Rdh5 are downregulated in optic cups and presumptive RPEs of Mitf-deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in Mitf-deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE.
视网膜色素上皮（RPE）细胞对视觉色素的再生是视觉的基础。我们在此表明，小眼症相关转录因子MITF在RPE细胞的发育和功能中起核心作用，它调控两个视觉循环基因的表达，即编码视黄醛结合蛋白-1（RLBP1）的Rlbp1和编码视黄醇脱氢酶-5（RDH5）的Rdh5。首先，我们发现Rlbp1和Rdh5在Mitf缺陷型小鼠胚胎的视杯和假定的RPE中表达下调。其次，对培养的人RPE细胞中MITF水平进行实验性操作会导致RLBP1和RDH5内源性水平的相应调节。第三，通过外源性供应9-顺式视黄醛，Mitf缺陷型小鼠中与视觉循环破坏相关的视网膜变性在结构和功能上均可得到部分纠正。我们得出结论，Rlbp1和Rdh5的表达严重依赖于RPE中功能性的Mitf，并表明MITF在控制RPE中的类视黄醇代谢过程中具有重要作用。
