Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Prog Retin Eye Res. 2018 Jul;65:1-27. doi: 10.1016/j.preteyeres.2018.03.002. Epub 2018 Mar 12.
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy. We highlight less-studied roles of DNA methylation and provide the RNA expression profiles of epigenetic enzymes in human and mouse retina in comparison to other tissues. We also review computational tools and emergent technologies to profile, analyze and integrate epigenetic information. We suggest implementation of editing tools and single-cell technologies to trace and perturb the epigenome for delineating its role in transcriptional regulation. Finally, we present our thoughts on exciting avenues for exploring epigenome in retinal metabolism, disease modeling, and regeneration.
复杂的生物过程，如器官发生和体内平衡，受到遗传程序的严格调控，这些遗传程序通过表观遗传因素进行微调，以确定细胞命运和/或对微环境做出反应。指导细胞分化和功能的基因调控网络通过 DNA、RNA 和蛋白质的修饰来调节和稳定。在这篇综述中，我们重点关注两种关键的表观遗传变化——DNA 甲基化和组蛋白修饰，并讨论它们对视网膜发育、衰老和疾病的贡献，特别是在年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变的背景下。我们强调了 DNA 甲基化的较少研究作用，并提供了人类和小鼠视网膜与其他组织相比的表观遗传酶的 RNA 表达谱。我们还回顾了用于分析和整合表观遗传信息的计算工具和新兴技术。我们建议实施编辑工具和单细胞技术来追踪和干扰表观基因组，以阐明其在转录调控中的作用。最后，我们提出了在探索视网膜代谢、疾病建模和再生中的表观基因组方面令人兴奋的途径的想法。
