Downregulation of miR-127-5p promotes idiopathic epiretinal membrane development via GLUL-mediated Müller cell activation.

Abstract

Idiopathic epiretinal membrane (iERM) represents a fibrocellular proliferation on retinal surface associated with vision loss, with underlying molecular mechanisms that remain undefined. The current work aimed to assess miR-127-5p for its role in the regulation of retinal Müller cell activity in iERM. We analyzed miRNA expression profiles in vitreous samples from iERM patients and controls. The regulatory relationship between miR-127-5p and GLUL (glutamine synthetase) was verified through dual-luciferase reporter assays and molecular studies. The functional effects of the miR-127-5p/GLUL axis manipulation were evaluated in rat retinal Müller cells using proliferation, migration, invasion, and apoptosis assays. miR-127-5p showed significant downregulation in iERM cases. miR-127-5p overexpression in retinal Müller cells suppressed their proliferative, invasive, and migratory capabilities, while inducing apoptotic cell death. GLUL was shown to be directly targeted by miR-127-5p and was upregulated in iERM patients. Knockdown of GLUL phenocopied the impacts of miR-127-5p overexpression, with its overexpression reversing miR-127-5p-associated suppressive effects on Müller cell behavior. These findings suggest miR-127-5p is a key modulator of iERM pathogenesis, functioning through its interaction with GLUL to control retinal Müller cell proliferation and migration. The miR-127-5p/GLUL axis might represent a novel target for iERM treatment.