A single cell atlas of circulating immune cells involved in diabetic retinopathy

Dan Liao; Wei Fan; Na Li; Ruonan Li; Xiaotang Wang; Jiangyi Liu; Hong Wang; Shengping Hou

doi:10.1016/j.isci.2024.109003

A single cell atlas of circulating immune cells involved in diabetic retinopathy

iScience. 2024 Jan 26;27(2):109003. doi: 10.1016/j.isci.2024.109003. eCollection 2024 Feb 16.

Authors

Dan Liao^{1

2}, Wei Fan¹, Na Li³, Ruonan Li¹, Xiaotang Wang¹, Jiangyi Liu¹, Hong Wang⁴, Shengping Hou^{1

5}

Affiliations

¹ The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
² The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
³ School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
⁴ Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
⁵ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.

Abstract

This study focused on examining the exact role of circulating immune cells in the development of diabetic retinopathy (DR). In vitro 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.

Keywords: Cell biology; Components of the immune system; Gene network; Transcriptomics.