METHODS: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia.
RESULTS: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples.
CONCLUSIONS: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.
方法:我们使用氧诱导的视网膜病变(OIR)模型研究了MDSCs在促进病理性血管生成中的作用,采用流式细胞术,免疫荧光,和smart-seq分析。然后,我们使用流式细胞术评估了患者血液样本中MDSCs的比例.此外,我们使用抗Gr-1单克隆抗体评估了MDSC耗竭对视网膜血管病变和视网膜小胶质细胞改变的影响.
结果:在OIR模型中,在II期(新生血管形成)期间,血液和视网膜组织中的MDSCs比例均升高.MDSCs的耗竭导致视网膜新生血管和血管闭塞减少,随着新生血管区域内小胶质细胞的减少。此外,与MDSCs相关的基因转录本分析显示血管内皮生长因子(VEGF)调节和炎症的激活。重要的是,ROP患儿血液样本中MDSC的比例较高.
结论:我们的结果表明,过多的MDSCs代表了眼部新生血管疾病的一个未被识别的特征,并负责视网膜血管炎症和血管生成,为眼部新生血管性疾病的新治疗方法提供了机会。