| Abstract: | We aimed to analyse the relative abundance of miR‐505 in age‐related macular degeneration (AMD) and elucidate its underlying mechanisms. Relative expression of miR‐505 was analysed by real‐time polymerase chain reaction (PCR). Macrophage polarization was characterized by measurement of molecular markers including Ym‐1, Arg‐1, TNF‐α and iNOS via both real‐time PCR and Western blot. Vascular endothelial growth factor (VEGF) content was determined by enzyme‐linked immunosorbent assay. Choroidal neovascularization (CNV) formation was evaluated by choroidal flat mount technique. The regulatory action of miR‐505‐5p on 3′UTR of Transmembrane Protein 229B (TMEM229B) was interrogated by luciferase reporter assay. miR‐505 was aberrantly upregulated in both AMD and laser‐induced choroidal neovascularization mouse model. Administration with miR‐505 specific inhibitor suppressed M2 polarization in CNV mice as indicated by decreasing both Ym‐1 and Arg‐1. Meanwhile, VEGF expression and CNV formation were greatly suppressed by miR‐505 inhibition as well. The similar phenotype was consolidated in Prostaglandin E2 (PGE2)‐stimulated bone marrow‐derived macrophages. At the molecular level, miR‐505‐5p directly targeted and negatively regulated TMEM229B expression, while forced ectopic expression of TMEM229B significantly rescued miR‐505‐imposed M2 polarization. Our data have uncovered the critical contribution of miR‐505 in AMD, which is predominantly mediated by downregulation of TMEM229B. |
