June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
A human circulating immune cell landscape in diabetic macular edema patients
Author Affiliations & Notes
  • Pengjuan Ma
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
  • Wen Shi
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
  • Jinguo Ye
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
  • Shida Chen
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Bingqian Liu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Rong Ju
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Yingfeng Zheng
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
  • Yizhi Liu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Pengjuan Ma, None; Wen Shi, None; Jinguo Ye, None; Shida Chen, None; Bingqian Liu, None; Rong Ju, None; Yingfeng Zheng, None; Yizhi Liu, None
  • Footnotes
    Support  National Natural Science Foundation of China (81530028; 81721003); the Guangdong Province Science & Technology Plan (2014B020228002); Local Innovative and Research Teams Project of Guangdong Pearl River Talents Programme; Clinical Innovation Research Programme of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR0201001); CAMS Innovation Fund for Medical Sciences (2019-I2M-5-005); Construction Project of High-Level Hospitals in Guangdong Province (303020107; 303010303058); the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2178. doi:
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    • Get Citation

      Pengjuan Ma, Wen Shi, Jinguo Ye, Shida Chen, Bingqian Liu, Rong Ju, Yingfeng Zheng, Yizhi Liu; A human circulating immune cell landscape in diabetic macular edema patients. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2178.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Inflammation plays an important role in diabetic macular edema (DME) and contribute to vascular permeability and edema by release of inflammatory cytokines, but little is known about the inflammatory roles of different circulating immune cells among DME patients. We utilized single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to clarify phenotype and function of peripheral immune cells in DME.

Methods : Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy donors. Single-cell RNA libraries were prepared using the Chromium Single Cell 5′ v2 Reagent (10x Genomics) kit. Raw sequence read quality was assessed using FastQC software. Cell Ranger Software was used to generate each sample’s gene counts and aggregate them together. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.

Results : We constructed a single-cell RNA atlas comprising 62,916 PBMCs collected from 4 healthy controls and 4 DME patients. We investigated the distribution of the major immune cell lineages, including monocytes, DCs, NK and T, and B cells, using uniform manifold approximation and projection (UMAP). We characterized the expression of canonical lineage markers and other genes specifically upregulated in each cell cluster. Our differential expression gene (DEG) analysis showed that monocytes were enriched of genes participating in the cytokine pathway and inflammation activation. Compared to healthy controls, CD14++ inflammatory monocytes in DME patients had high expression levels of inflammatory genes such as IL1β, TNF, JUN, FOS, and NF-κB; and higher expression levels of chemokines, including CCL3, CCL4, and CXCR4. Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that TNF, interleukin signaling, and NF-κB signaling pathways were enhanced in DME patients.

Conclusions : We reveal a landscape of peripheral blood immune cell subsets in DME patients. CD14++ monocytes exhibit features of chronic stimulation and participate in chronic inflammation through producing inflammatory cytokines. Therapeutic interventions targeting chronic inflammation in monocytes may lead to improved outcomes in patients with diabetic macular edema.

This is a 2021 ARVO Annual Meeting abstract.

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