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Updated: Jun 19, 2026

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Tear-Derived Exosomal miR-15a as New Diagnostic Tool for Diabetic Retinopathy
Published on: December 30, 2025
Integrated Bioinformatics and Explainable Machine Learning Analyses Reveal Mesenchymal Stem Cell Exosome-Related
Liu Zheng1, Jiaojiao Jiang1, Jinqing Li1
1Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, China.
Summary
Researchers identified YBX1 and PSMA7 from mesenchymal stem cell-derived exosomes (MSCs-Exo) as potential biomarkers for diabetic retinopathy (DR). These genes showed reduced expression in DR mouse models, suggesting diagnostic utility.
Area of Science:
- Biochemistry and Molecular Biology
- Genomics and Bioinformatics
- Ophthalmology and Vision Science
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss, necessitating novel diagnostic biomarkers.
- Mesenchymal stem cell-derived exosomes (MSCs-Exo) are increasingly recognized for their therapeutic and diagnostic potential in various diseases.
- Identifying specific molecules within MSCs-Exo could offer new avenues for DR detection and management.
Purpose of the Study:
- To identify potential diagnostic biomarkers for diabetic retinopathy (DR) from genes within mesenchymal stem cell-derived exosomes (MSCs-Exo).
- To investigate the role of these identified genes in the pathogenesis and immune dysregulation associated with DR.
Main Methods:
- Integrated DR transcriptome data with MSCs-Exo protein datasets.
- Employed bioinformatics analyses including weighted gene coexpression network analysis, Mfuzz clustering, and machine learning (LASSO, Random Forest).
- Validated key gene candidates (YBX1, PSMA7) using immunohistochemistry and Western blotting in DR mouse models, alongside functional enrichment, immune infiltration, and single-cell RNA sequencing analyses.
Main Results:
- Identified 16 hub genes within MSCs-Exo, pinpointing YBX1 and PSMA7 as central players using interpretable machine learning.
- Developed a predictive DR diagnostic model with modest efficacy (AUC > 0.7).
- Confirmed significantly reduced protein expression of YBX1 and PSMA7 in retinal tissues of DR mice (P < 0.05), linking them to protein/amino acid metabolism and immune dysregulation, particularly in CD4T memory cells.
Conclusions:
- YBX1 and PSMA7 derived from MSCs-Exo show promise as potential novel biomarkers for diabetic retinopathy.
- These findings highlight the involvement of YBX1 and PSMA7 in DR pathogenesis and immune responses.
- Further research is warranted to establish the clinical applicability and therapeutic significance of YBX1 and PSMA7 in DR management.
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Overview of Exosomes
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
