Epitranscriptomic investigation of myopia-associated RNA editing in the retina

Abstract

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development.