Transcriptome profiling of the rat retina after optic nerve transection.
Transcriptome profiling of the rat retina after optic nerve transection.
复制标题
DOI：
10.1038/srep28736
复制
发表时间：
2016-06-29
影响因子：
4.6
通讯作者：
Nakazawa T
中科院分区：
文献类型：
--
作者：
Yasuda M;Tanaka Y;Omodaka K;Nishiguchi KM;Nakamura O;Tsuda S;Nakazawa T
青光眼是一组眼部疾病，其特征在于视神经乳头（ONH）的轮廓改变，伴随相应的视野缺损和视网膜神经节细胞（RGC）的进行性丧失。这种进行性RGC死亡被认为起源于ONH中轴突束压缩引起的轴突损伤。然而，轴突损伤诱导的RGC死亡的分子病理机制尚未得到很好的理解。在这里，我们使用RNA测序（RNA-seq）来检查视神经横断（ONT）后2天大鼠视网膜中的转录组变化，然后使用计算技术来预测转录调控网络中产生的变化。RNA-seq共发现267个差异表达基因，其中218个被注释，49个未注释。我们还确定了差异表达的转录本，包括潜在的新亚型。计算机途径分析预测CREB 1是最重要的上游调节因子。因此，本研究确定了可能参与轴突损伤病理机制的基因和途径。我们相信，我们的数据应该作为一个有价值的资源，以了解定义轴突损伤驱动的RGC死亡的分子过程，并发现新的青光眼治疗靶点。
Glaucoma is a group of eye diseases characterized by alterations in the contour of the optic nerve head (ONH), with corresponding visual field defects and progressive loss of retinal ganglion cells (RGCs). This progressive RGC death is considered to originate in axonal injury caused by compression of the axon bundles in the ONH. However, the molecular pathomechanisms of axonal injury-induced RGC death are not yet well understood. Here, we used RNA sequencing (RNA-seq) to examine transcriptome changes in rat retinas 2 days after optic nerve transection (ONT), and then used computational techniques to predict the resulting alterations in the transcriptional regulatory network. RNA-seq revealed 267 differentially expressed genes after ONT, 218 of which were annotated and 49 unannotated. We also identified differentially expressed transcripts, including potentially novel isoforms. An in silico pathway analysis predicted that CREB1 was the most significant upstream regulator. Thus, this study identified genes and pathways that may be involved in the pathomechanisms of axonal injury. We believe that our data should serve as a valuable resource to understand the molecular processes that define axonal injury-driven RGC death and to discover novel therapeutic targets for glaucoma.