MDSCs promote pathological angiogenesis in ocular neovascular disease

被引:2
作者
Wu, Xiaojun [1 ,2 ,3 ]
Zhong, Limei [4 ]
Yu, Jun [3 ]
Wang, Ning [1 ,2 ]
Bu, Shimiao [3 ]
Wang, Huijuan [3 ]
Zhang, Jie [5 ]
Luo, Xianqiong [1 ,2 ]
Liu, Yufeng [3 ]
Nie, Chuan [1 ,2 ]
机构
[1] Guangdong Women & Children Hosp, Neonatol Dept, Guangzhou 510000, Guangdong, Peoples R China
[2] Guangdong Neonatal ICU Med Qual Control Ctr, Natl Key Clin Specialty Construct Project, Guangzhou 510000, Guangdong, Peoples R China
[3] South China Univ Technol, Guangzhou Peoples Hosp 1, Affiliated Hosp 2, Ctr Med Res Innovat & Translat, Guangzhou 510005, Guangdong, Peoples R China
[4] Guangdong Second Prov Gen Hosp, Dept Lab Med, Guangzhou 510317, Guangdong, Peoples R China
[5] Guangdong Women & Children Hosp, Dept Rehabil, Guangzhou 510000, Guangdong, Peoples R China
关键词
Retinal neovascularization; Oxygen-induced Retinopathy; Myeloid derived suppressor cells; Retinopathy of Prematurity; OXYGEN-INDUCED RETINOPATHY; SUPPRESSOR-CELLS; MOUSE; PATHOPHYSIOLOGY;
D O I
10.1016/j.biopha.2024.117222
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: 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. Method: 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 vasoobliteration, 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. Conclusion: 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.
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页数:12
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