MiR-423-5p promotes Müller cell activation via targeting NGF signaling in diabetic retinopathy

Abstract

AimsDiabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus and one of the major causes of visual impairment and blindness in industrialized countries. The early neuro-glial perturbations, especially retinal Müller cells (rMC) activation, intimately associated with the vascular alterations. MicroRNAs (miRNAs) have been reported to play critical roles in the progression of DR. Here, we aimed to further explore the role and underlying mechanism of miR-423-5p in Müller cell activation in streptozotocin (STZ)-induced diabetic mice and oxygen-induced retinopathy (OIR) model. Materials and methodsRetinal histology, optical coherence tomography (OCT) and biochemical markers were assessed. Key findingsOur data revealed that the expression of miR-423-5p was significantly increased under high-glucose environment. We also demonstrated that miR-423-5p overexpression markedly accelerated retinal vascular leakage, leukocytosis, and rMC activation. This response was ameliorated in animals pre-treated with the inhibition of miR-423-5p. Specifically, miR-423-5p bound to the nerve growth factor (NGF) 3′ UTR region to induce its silencing. NGF inhibition significantly promoted retinal microvascular dysfunction. SignificanceThese findings demonstrate that miR-423-5p is a critical miRNA that promotes microvascular dysfunction in DR.