Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Departments of Ophthalmology, Wilmer Eye Institute, Neuroscience, Molecular Biology and Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Cold Spring Harb Perspect Med. 2023 Oct 3;13(10):a041313. doi: 10.1101/cshperspect.a041313.
Alternative splicing is a fundamental and highly regulated post-transcriptional process that enhances transcriptome and proteome diversity. This process is particularly important in neuronal tissues, such as the retina, which exhibit some of the highest levels of differentially spliced genes in the body. Alternative splicing is regulated both temporally and spatially during neuronal development, can be cell-type-specific, and when altered can cause a number of pathologies, including retinal degeneration. Advancements in high-throughput sequencing technologies have facilitated investigations of the alternative splicing landscape of the retina in both healthy and disease states. Additionally, innovations in human stem cell engineering, specifically in the generation of 3D retinal organoids, which recapitulate many aspects of the in vivo retinal microenvironment, have aided studies of the role of alternative splicing in human retinal development and degeneration. Here we review these advances and discuss the ongoing development of strategies for the treatment of alternative splicing-related retinal disease.
选择性剪接是一种基本且高度受调控的转录后过程，可增强转录组和蛋白质组的多样性。该过程在神经组织中尤为重要，例如视网膜，其表现出体内差异剪接基因水平最高的组织之一。在神经元发育过程中，选择性剪接受到时间和空间的调节，具有细胞类型特异性，并且当发生改变时，会导致多种病理学，包括视网膜变性。高通量测序技术的进步促进了对健康和疾病状态下视网膜选择性剪接景观的研究。此外，人类干细胞工程的创新，特别是在生成 3D 视网膜类器官方面，这些类器官可再现体内视网膜微环境的许多方面，有助于研究选择性剪接在人类视网膜发育和变性中的作用。在这里，我们回顾了这些进展，并讨论了治疗与选择性剪接相关的视网膜疾病的策略的持续发展。
