Liao Dan, Fan Wei, Li Na, Li Ruonan, Wang Xiaotang, Liu Jiangyi, Wang Hong, Hou Shengping
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
iScience. 2024 Jan 26;27(2):109003. doi: 10.1016/j.isci.2024.109003. eCollection 2024 Feb 16.
This study focused on examining the exact role of circulating immune cells in the development of diabetic retinopathy (DR). co-culture experiments showed that peripheral blood mononuclear cells (PBMCs) from patients with type 1 DR crucially modulated the biological functions of human retinal microvascular endothelial cells (HRMECs), consequently disrupting their normal functionality. Single-cell RNA sequencing (scRNA-seq) study revealed unique differentially expressed genes and pathways in circulating immune cells among healthy controls, non-diabetic retinopathy (NDR) patients, and DR patients. Of significance was the observed upregulation of JUND in each subset of PBMCs in patients with type 1 DR. Further studies showed that downregulating JUND in DR patient-derived PBMCs led to the amelioration of HRMEC dysfunction. These findings highlighted the notable alterations in the transcriptomic patterns of circulating immune cells in type 1 DR patients and underscored the significance of JUND as a key factor for PBMCs in participating in the pathogenesis of DR.
本研究聚焦于探讨循环免疫细胞在糖尿病视网膜病变(DR)发展过程中的具体作用。共培养实验表明,1型DR患者的外周血单核细胞(PBMCs)对人视网膜微血管内皮细胞(HRMECs)的生物学功能具有关键调节作用,从而破坏其正常功能。单细胞RNA测序(scRNA-seq)研究揭示了健康对照、非糖尿病视网膜病变(NDR)患者和DR患者循环免疫细胞中独特的差异表达基因和信号通路。值得注意的是,在1型DR患者的每个PBMC亚群中均观察到JUND的上调。进一步研究表明,下调DR患者来源的PBMCs中的JUND可改善HRMEC功能障碍。这些发现突出了1型DR患者循环免疫细胞转录组模式的显著改变,并强调了JUND作为PBMCs参与DR发病机制的关键因素的重要性。