Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Yan Ma
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China
Yun Bai
College of Information Science, Shanghai Ocean University, Shanghai 201306, China
Qiuyang Zhang
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China
Ya Zhao
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Jiao Xia
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Mudi Yao
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Corresponding author
Summary: Inflammation-mediated crosstalk between neuroglial cells and endothelial cells (ECs) is a fundamental feature of many vascular diseases. Nevertheless, the landscape of inflammatory processes during diabetes-induced microvascular dysfunction remains elusive. Here, we applied single-cell RNA sequencing to elucidate the transcriptional landscape of diabetic retinopathy (DR). The transcriptome characteristics of microglia and ECs revealed two microglial subpopulations and three EC populations. Exploration of intercellular crosstalk between microglia and ECs showed that diabetes-induced interactions mainly participated in the inflammatory response and vessel development, with colony-stimulating factor 1 (CSF1) and CSF1 receptor (CSF1R) playing important roles in early cell differentiation. Clinically, we found that CSF1/CSF1R crosstalk dysregulation was associated with proliferative DR. Mechanistically, ECs secrete CSF1 and activate CSF1R endocytosis and the CSF1R phosphorylation-mediated MAPK signaling pathway, which elicits the differentiation of microglia and triggers the secretion of inflammatory factors, and subsequently foster angiogenesis by remodeling the inflammatory microenvironment through a positive feedback mechanism.
