Neonatology Department, Guangdong Women and Children Hospital, Guangzhou, Guangdong 510000, China; National Key Clinical Specialty Construction Project/Guangdong Neonatal ICU Medical Quality Control Center, Guangzhou, Guangdong 510000, China; Center for Medical Research on Innovation and Translation, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510005, China.
Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, China.
Biomed Pharmacother. 2024 Sep;178:117222. doi: 10.1016/j.biopha.2024.117222. Epub 2024 Jul 31.
Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target.
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.
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.
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.
眼部新生血管疾病是导致视力丧失的主要原因，但目前缺乏有效的预防治疗方法。最近的研究强调了免疫细胞在新生血管性视网膜病变中的重要作用。髓系来源的抑制细胞（MDSCs）促进新生血管的形成，但尚不清楚它们是否参与病理性新生血管形成，以及它们是否有望成为治疗靶点。
我们使用氧诱导视网膜病变（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，我们还评估了使用抗 Gr-1 单克隆抗体耗竭 MDSC 对视网膜血管病变和视网膜小胶质细胞变化的影响。
在 OIR 模型中，在第二期（新生血管形成期），血液和视网膜组织中 MDSCs 的比例升高。MDSC 耗竭导致视网膜新生血管形成和血管闭塞减少，新生血管化区域内的小胶质细胞减少。此外，与 MDSCs 相关的基因转录物分析表明血管内皮生长因子（VEGF）调节和炎症的激活。重要的是，ROP 婴儿的血液样本中 MDSCs 的比例更高。
我们的研究结果表明，过多的 MDSCs 是眼部新生血管疾病的一个未被认识的特征，可能导致视网膜血管炎症和血管生成，为眼部新生血管疾病的新治疗方法提供了机会。
