Journal of translational medicine · 2025
Targeting macrophage to myofibroblast transition by circ_0001103 for subretinal fibrosis treatment.
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Zhang Qi, Lu Bing, He Lei, Fang Kai, Zhu Xiaolong, Chen Tianbing, Zhu Yingying, Liu Yinping, Zhang Pengfei
Аннотация
PURPOSE: Subretinal fibrosis is an important cause of visual loss in age-related macular degeneration, but its mechanism remains unclear. This study aims to investigate the role of macrophage-to-myofibroblast transition (MMT) in the formation of subretinal fibrosis and assess whether circ_0001103 can regulate the formation of subretinal fibrosis by regulating MMT.
METHODS: Subretinal fibrosis was induced in C57BL/6J mice by laser induction. The expression profiles of circRNAs in a choroidal neovascularization (CNV) and subretinal fibrosis mice model were accessed via microarray analysis. MMT was induced by TGF-β1 (2.5 ng/ml, 48 h). Immunohistochemistry was used to assess macrophages (F4/80), MMT (α-SMA) and fibrovascular lesions (collagenI and Isolectin B4) in vivo. The interaction between circ_0001103, miR-7240-5p, and SLC9A was assessed using a dual-luciferase reporter assay, FISH, RNA immunoprecipitation assay, qRT-PCR and western blot. Finally, immunofluorescence, paraffin section and choroidal flatmounts were used to observe the changes of MMT, subretinal fibrosis and CNV after the intervention of circ_0001103 by intravitreal injection on day 7 after laser induction in mice.
RESULTS: The results revealed that 58 circRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (p < 0.05, fold change > 2.0). Additionally, circ_0001103 increased in MMT and subretinal fibrosis mice. Circ_0001103 can sponge miR-7240-5p targeting SLC9A to modulate MMT in vitro. Inhibition of circ_0001103 can suppress MMT, subretinal fibrosis and CNV leakage.
CONCLUSION: circ_0001103 sponge adsorption miR-7240-5p regulates SLC9A1-mediated MMT and subretinal fibrosis. Inhibition of circ_0001103 can suppress subretinal fibrosis and CNV leakage by inhibiting MMT.
METHODS: Subretinal fibrosis was induced in C57BL/6J mice by laser induction. The expression profiles of circRNAs in a choroidal neovascularization (CNV) and subretinal fibrosis mice model were accessed via microarray analysis. MMT was induced by TGF-β1 (2.5 ng/ml, 48 h). Immunohistochemistry was used to assess macrophages (F4/80), MMT (α-SMA) and fibrovascular lesions (collagenI and Isolectin B4) in vivo. The interaction between circ_0001103, miR-7240-5p, and SLC9A was assessed using a dual-luciferase reporter assay, FISH, RNA immunoprecipitation assay, qRT-PCR and western blot. Finally, immunofluorescence, paraffin section and choroidal flatmounts were used to observe the changes of MMT, subretinal fibrosis and CNV after the intervention of circ_0001103 by intravitreal injection on day 7 after laser induction in mice.
RESULTS: The results revealed that 58 circRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (p < 0.05, fold change > 2.0). Additionally, circ_0001103 increased in MMT and subretinal fibrosis mice. Circ_0001103 can sponge miR-7240-5p targeting SLC9A to modulate MMT in vitro. Inhibition of circ_0001103 can suppress MMT, subretinal fibrosis and CNV leakage.
CONCLUSION: circ_0001103 sponge adsorption miR-7240-5p regulates SLC9A1-mediated MMT and subretinal fibrosis. Inhibition of circ_0001103 can suppress subretinal fibrosis and CNV leakage by inhibiting MMT.