A MicroRNA, mir133b, suppresses melanopsin expression mediated by failure dopaminergic amacrine cells in RCS rats
A MicroRNA, mir133b, suppresses melanopsin expression mediated by failure dopaminergic amacrine cells in RCS rats
复制标题
MicroRNA mir133b 抑制 RCS 大鼠多巴胺能无长突细胞衰竭介导的黑视蛋白表达
DOI：
10.1016/j.cellsig.2011.10.017
复制
发表时间：
2012-03-01
影响因子：
4.8
通讯作者：
Yin, Zheng Qin
中科院分区：
文献类型：
--
作者：
Li, Yaochen;Li, Chunshi;Yin, Zheng Qin
色素黑视蛋白和含黑视蛋白的视网膜神经节细胞（mRGCs或ipRGCs）代表了视觉领域一个崭新的、令人兴奋的研究方向。虽然黑视素对光不太敏感，空间分辨率也低得多，但mRGC具有独特的能力，可以通过视网膜下丘脑束（RHT）投射到大脑区域，并直接与大脑沟通。不幸的是，黑视蛋白在许多急性和慢性视网膜疾病中呈现较低的表达水平。黑视素表达的分子机制尚未真正了解。microRNA在发育调控中发挥重要作用。最重要的是，microRNA生物学与一系列不同的细胞过程的联系正在出现，这些过程从增殖、凋亡和恶性转化到神经元发育和命运的指定。我们采用皇家外科学院（RCS）大鼠作为动物模型，通过实时定量逆转录聚合酶链反应（RT-PCR），使用一组miRNA来研究调节黑视素表达的潜在分子机制。我们鉴定了一种microRNA，mir 133 b，其在视网膜多巴胺能无长突细胞中特异性表达，并且在RCS大鼠视网膜变性的早期阶段表达显著增加。mir 133 b的过表达下调RCS大鼠视网膜多巴胺能无长突细胞中重要的转录因子Pitx 3的表达，使无长突细胞在强脉冲光下分层功能受损。此外，缺乏mir 133 b的多巴胺能无长突细胞表现为TH表达和多巴胺分泌减少，导致mRGCs树突不能分层进入INL，从而导致无长突细胞与mRGCs之间的正确连接减少。我们的研究表明，过表达mir 133 b和下调Pitx 3抑制多巴胺能无长突细胞的成熟和功能，而过表达mir 133 b降低TH和D2受体的表达以及多巴胺的产生，最终导致黑视素的表达减少。(C)2011 Elsevier Inc. All rights reserved.
The photopigment melanopsin and melanopsin-containing RGCs (mRGCs or ipRGCs) represent a brand-new and exciting direction in the field of visual field. Although the melanopsin is much less sensitive to light and has far less spatial resolution, mRGCs have the unique ability to project to brain areas by the retinohypothalamic tract (RHT) and communicate directly with the brain. Unfortunately, melanopsin presents lower expression levels in many acute and chronic retinal diseases. The molecular mechanisms underlying melanopsin expression are not yet really understood. MicroRNAs play important roles in the control of development. Most importantly, the link of microRNA biology to a diverse set of cellular processes, ranging from proliferation, apoptosis and malignant transformation to neuronal development and fate specification is emerging. We employed Royal College of Surgeon (RCS) rats as animal model to investigate the underlying molecular mechanism regulating melanopsin expression using a panel of miRNA by quantitative real-time reverse transcription polymerase chain reaction. We identified a microRNA, mir133b, that is specifically expressed in retinal dopaminergic amacrine cells as well as markedly increased expression at early stage during retinal degeneration in RCS rats. The overexpression of mir133b downregulates the important transcription factor Pitx3 expression in dopaminergic amacrine cells in RCS rats retinas and makes amacrine cells stratification deficit in IPL Furthermore, deficient dopaminergic amacrine cells presented decreased TH expression and dopamine production, which lead to a failure to direct mRGCs dendrite to stratify and enter INL and lead to the reduced correct connections between amacrine cells and mRGCs. Our study suggested that overexpression of mir133b and downregulated Pitx3 suppress maturation and function of dopaminergic amacrine cells, and overexpression of mir133b decreased TH and D2 receptor expression as well as dopamine production, which finally resulted in reduced melanopsin expression. (C) 2011 Elsevier Inc. All rights reserved.