MiR-505 promotes M2 polarization in choroidal neovascularization model mice by targeting transmembrane protein 229B.

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 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.

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