Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration

Lingzi Wu, Lei Zhou, Jinying An, Xianfeng Shao, Hui Zhang, Chunxi Wang, Guixia Zhao, Shuang Chen, Xuexue Cui, Xinyi Zhang, Fuhua Yang, Xiaorong Li, Xiaomin Zhang (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Background
Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging.

Methods
Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents.

Results
In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified.

Conclusions
This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents.
Original languageEnglish
Article number388
Number of pages20
JournalJournal of Translational Medicine
Volume21
Issue number1
DOIs
Publication statusPublished - 15 Jun 2023

Keywords

  • Plasma
  • Small extracellular vesicles
  • Large extracellular vesicles
  • Uveitis
  • Scleritis
  • Proteomic profiles
  • Biomarkers
  • Connectivity map

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