Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sci Rep. 2018 Feb 14;8(1):3040. doi: 10.1038/s41598-018-21104-7.
Age-related macular degeneration (AMD) predominantly affects the retina and retinal pigment epithelium in the posterior eye. While there are numerous studies investigating the non-coding transcriptome of retina and RPE, few significant differences between AMD and normal tissues have been reported. Strand specific RNA sequencing of both peripheral retina (PR) and RPE-Choroid-Sclera (PRCS), in both AMD and matched normal controls were generated. The transcriptome analysis reveals a highly significant and consistent impact on anti-sense transcription as well as moderate changes in the regulation of non-coding (sense) RNA. Hundreds of genes that do not express anti-sense transcripts in normal PR and PRCS demonstrate significant anti-sense expression in AMD in all patient samples. Several pathways are highly enriched in the upregulated anti-sense transcripts-in particular the EIF2 signaling pathway. These results call for a deeper exploration into anti-sense and noncoding RNA regulation in AMD and their potential as therapeutic targets.
年龄相关性黄斑变性（AMD）主要影响眼后段的视网膜和视网膜色素上皮。虽然有许多研究调查视网膜和 RPE 的非编码转录组，但报道的 AMD 与正常组织之间的显著差异很少。对 AMD 和匹配的正常对照组的外周视网膜（PR）和 RPE-脉络膜-巩膜（PRCS）进行了链特异性 RNA 测序。转录组分析显示，反义转录受到高度显著和一致的影响，非编码（有义）RNA 的调节也发生了适度变化。在正常的 PR 和 PRCS 中不表达反义转录本的数百个基因在所有患者样本中都表现出明显的反义表达。几个途径在上调的反义转录本中高度富集 - 特别是 EIF2 信号通路。这些结果呼吁更深入地研究 AMD 中的反义 RNA 和非编码 RNA 调节及其作为治疗靶点的潜力。
