LncRNA DANCR Activates p38/mTOR-Mediated Autophagy via ANXA2 to Exacerbate Oxygen-Induced Retinal Neovascularization in Mice.

Abstract

The mouse model of oxygen-induced retinopathy (OIR) recapitulates key pathological features observed in human retinal neovascular diseases, including retinopathy of prematurity (ROP). Recent research has highlighted the involvement of long noncoding RNAs (lncRNAs) in retinal neovascular diseases, but their specific roles remain unclear. Using human retinal microvascular endothelial cells (ECs) and OIR mice, we found upregulation of lncRNA DANCR in ROP models. DANCR overexpression enhanced EC proliferation, migration, and angiogenesis, while suppressing apoptosis via autophagy activation. RNA pull-down and RNA immunoprecipitation assays confirmed that DANCR directly bound to Annexin A2 (ANXA2). Critically, ANXA2 knockdown partially reversed the DANCR-driven pro-angiogenic effects by upregulating the p38 MAPK/mTOR pathway. Intravitreal RNA interference-DANCR reduced ANXA2 expression, attenuated the severity of retinal vascular and glial cell pathology, and improved visual function. Collectively, lncRNA DANCR exacerbated retinal neovascularization by activating autophagy via the ANXA2/p38 MAPK/mTOR axis, identifying this pathway as a novel therapeutic target for ROP.