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.

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

“…Similarly, the accumulation of SM causes different neurological disorders. SM buildup following SMase deficiency is associated with Parkinson’s disease ( Pan et al, 2023 ). Reduced levels of aSMase prevent autophagy, whereas reduced levels of nSMase prevent stem cell differentiation; both mechanisms impair neurogenesis ( Signorelli et al, 2021 ).…”

Temporal landscape and translational regulation of A-to-I RNA editing in mouse retina development

“…Proper developmental regulation of the retina is imperative for maintaining normal vision and ocular health, as abnormalities can lead to visual impairments and retinal pathologies. Several studies have highlighted the significant implications of A-to-I editing in the retina [16][17][18][19]. For instance, Drosophila melanogaster lacking the dADAR enzyme, which catalyzes A-to-I editing, exhibited structural abnormalities in the retina [20].…”