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Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas.

Authors
  • Sun, Licheng1
  • Wang, Ruonan1
  • Hu, Guangyi1
  • Liu, Huazhen1
  • Lv, Kangjia1
  • Duan, Yi1
  • Shen, Ning1
  • Wu, Jiali1
  • Hu, Jing1
  • Liu, Yujuan1
  • Jin, Qihuang2
  • Zhang, Fang3
  • Xu, Xun4
  • 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China; National Clinical Research Center for Eye Diseases, 200080, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, 200080, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, 200080, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, 200080, Shanghai, China. , (China)
  • 2 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China; National Clinical Research Center for Eye Diseases, 200080, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, 200080, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, 200080, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, 200080, Shanghai, China. Electronic address: [email protected] , (China)
  • 3 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China; National Clinical Research Center for Eye Diseases, 200080, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, 200080, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, 200080, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, 200080, Shanghai, China. Electronic address: [email protected] , (China)
  • 4 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China; National Clinical Research Center for Eye Diseases, 200080, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, 200080, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, 200080, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, 200080, Shanghai, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Experimental Eye Research
Publisher
Elsevier
Publication Date
Sep 01, 2021
Volume
210
Pages
108718–108718
Identifiers
DOI: 10.1016/j.exer.2021.108718
PMID: 34364890
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Diabetic retinopathy (DR) is an irreversible and progressive diabetic complication leading to visual impairment, even blindness. Due to the delicate and complicated structure of the retina, the pathology of DR has not been completely elucidated yet. We constructed a transcriptome atlas of >14,000 single cells from healthy and streptozotocin (STZ)-induced diabetic murine retinas to decipher pathological alterations of DR. We found four stress-inducible genes Cirbp, Rmb3, Mt1 and Mt2 commonly induced in most types of retinal cells. Bipolar cells were little affected on both number and gene expression. Diabetes increased expression of inflammatory factor genes in retinal microglia, and stimulated expression of immediate early genes (IEGs) in retinal astrocytes. A large number of genes were deregulated in diabetic vascular endothelial cells (ECs), and the differentially expressed genes were paired to the pathways functioning in metabolism, shear stress and vascular permeability. These pathways were mapped by more deregulated genes in a subpopulation of ECs specifically presented in diabetic retinas (diabetic retinal ECs, DRECs). Moreover, several inflammation pathways were activated in DRECs, and the most significant one is the IL-17 signaling pathway. According to the EC markers, DRECs were mainly capillary ECs, confirmed by immunofluorescent staining of S100a9, a target gene of the IL-17 signaling pathway. This study deciphered pathological alterations of DR, and provided clues for potential targets for DR therapy. Copyright © 2021 Elsevier Ltd. All rights reserved.

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