circMettl9 promotes retinal mitochondrial dysfunction and apoptosis via miR-10a-5p/Bcl2l11 pathway.

Abstract

CircRNAs are critical regulators in retinal neural tissues, yet the functions of most retina-enriched members remain unknown. circMettl9, highly expressed in the mouse retina, shows declining expression during postnatal development. Sustained circMettl9 overexpression in adult retinas via AAV-mediated subretinal injection triggers Müller gliosis, secretion of pro-inflammatory cytokines and retinal functional impairment: elevated GFAP levels and abnormal electroretinogram (ERG) responses were detected, while overt structural abnormalities were absent. Mechanistically, circMettl9 drives mitochondrial dysfunction, oxidative stress elevation and caspase-3 activation to promote retinal cell apoptosis via the circMettl9/miR-10a-5p/Bcl2l11 axis. Our study is the first to clarify the biological role of circMettl9 in mouse retina, providing novel theoretical insights and potential therapeutic targets for retinal diseases.