Affiliation:
1. Department of Ophthalmology Eye and ENT Hospital of Fudan University Shanghai China
2. Shanghai Key Laboratory of Visual Impairment and Restoration Eye and ENT Hospital of Fudan University Shanghai China
3. Department of Ophthalmology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China
4. Research Center Eye and ENT Hospital of Fudan University Shanghai China
Abstract
AbstractBackgroundCircular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA‐expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light‐induced photoreceptor apoptosis.MethodsSprague–Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light‐induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT‐PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin–eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry.ResultsWe identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous‐system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a‐wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis.ConclusionsCircUvrag knockdown attenuated light‐induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.