Donato Luigi, D'Angelo Rosalia, Alibrandi Simona, Rinaldi Carmela, Sidoti Antonina, Scimone Concetta
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy.
Department of Biomolecular Strategies, Genetics and Avant-Garde Therapies, I.E.ME.S.T., 90139 Palermo, Italy.
Antioxidants (Basel). 2020 Apr 10;9(4):307. doi: 10.3390/antiox9040307.
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.
氧化应激是与生活方式相关疾病和遗传性疾病的主要诱因之一。其中，诸如年龄相关性黄斑变性和视网膜色素变性等遗传性视网膜营养不良症，众所周知易受氧化应激影响。为了更好地理解高活性氧水平如何参与视网膜营养不良症的发病和进展，我们进行了一项全RNA测序实验。该实验包括比较暴露于氧化剂N-视黄叉基-N-视黄基乙醇胺（A2E）的人视网膜色素上皮细胞转录组图谱，时间点为基础时间点后的两个时间点（3小时和6小时）。用A2E处理导致基因表达和剪接事件出现显著差异，涉及几个可能与视网膜变性相关的新途径。我们发现了10个不同的涉及差异表达和差异可变剪接基因的途径簇，并突出了那些可能描绘由氧化应激诱导条件所决定的更详细情况的子途径。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、生理或病理自噬、细胞死亡诱导和视网膜细胞拯救的调节和/或改变是失调最严重的途径。我们的结果可能是朝着发现将氧化应激与视网膜营养不良症病因联系起来的不明分子机制迈出的重要一步。
