Microglia-endothelial cross-talk regulates diabetes-induced retinal vascular dysfunction through remodeling inflammatory microenvironment

Shuai Ben; Yan Ma; Yun Bai; Qiuyang Zhang; Ya Zhao; Jiao Xia; Mudi Yao

iScience (Mar 2024)

Microglia-endothelial cross-talk regulates diabetes-induced retinal vascular dysfunction through remodeling inflammatory microenvironment

Shuai Ben,
Yan Ma,
Yun Bai,
Qiuyang Zhang,
Ya Zhao,
Jiao Xia,
Mudi Yao

Affiliations

Shuai Ben: 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

Journal volume & issue: Vol. 27, no. 3
p. 109145

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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