Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies
Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies
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DOI：
10.3390/antiox9040307
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发表时间：
2020-04-01
期刊：
影响因子：
7
通讯作者：
Scimone, Concetta
中科院分区：
文献类型：
--
作者：
Donato, Luigi;D'Angelo, Rosalia;Scimone, Concetta
氧化应激是生活方式相关疾病和遗传疾病的主要诱因之一。其中，遗传性视网膜营养不良，如年龄相关性黄斑变性和色素性视网膜炎，是众所周知的是易受氧化应激。为了更好地了解高活性氧水平可能参与视网膜营养不良的发病和进展，我们进行了整个RNA-Seq实验。它包括比较暴露于氧化剂N-亚视黄基-N-视黄乙醇胺（A2 E）的人视网膜色素上皮细胞中的转录组谱，考虑基础时间点后的两个时间点（3 h和6 h）。用A2 E治疗确定了基因表达和剪接事件的相关差异，涉及可能与视网膜变性相关的几种新途径。我们发现了10个不同的通路簇，涉及差异表达和差异选择性剪接基因，并强调了子通路，这些子通路可以描述由氧化应激诱导的条件决定的更详细的情况。特别是，血管生成、细胞外基质完整性、类异戊二烯介导的反应、生理或病理性自噬、细胞死亡诱导和视网膜细胞拯救的调节和/或改变代表了最失调的途径。我们的研究结果可能代表了一个重要的一步，发现不清楚的分子机制连接氧化应激和视网膜营养不良的发病机制。
Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes' profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.