Casey J. Keuthan1, Sadik Karma1 and Donald J. Zack2 1Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA 2Departments of Ophthalmology, Wilmer Eye Institute, Neuroscience, Molecular Biology and Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA Correspondence: donzackgmail.com

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.