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Updated: Mar 7, 2026
Tear-Derived Exosomal miR-15a as New Diagnostic Tool for Diabetic Retinopathy
Published on: December 30, 2025
Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress
Tengku Ain Kamalden1, Anne M Macgregor-Das2, Sangeetha Marimuthu Kannan2,3
11 University of Malaya Eye Research Centre, Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .
Aims:
MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.
Results:
We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
Innovation:
This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
Conclusion:
Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
Insights
Increased microRNAs (miRNAs) in type 2 diabetes (T2D) plasma, specifically miR-15a from pancreatic exosomes, drive retinal injury and cell death by targeting Müller cells. This reveals a novel mechanism of diabetes-related cell communication and damage.
Area of Science:
- Endocrinology
- Molecular Biology
- Cellular Biology
Background:
- MicroRNAs (miRNAs) are noncoding RNAs regulating gene expression in type 2 diabetes (T2D) pathogenesis.
- The role of miRNAs in mediating long-distance cellular communication in T2D is not well understood.
Purpose of the Study:
- To investigate the function of exosomal miRNAs in the context of T2D.
- To explore how miRNAs contribute to T2D pathogenesis through intercellular communication.
Main Methods:
- Quantification of plasma miR-15a in diabetic patients.
- In vitro studies using rat pancreatic beta-cell (INS-1) line cultured in high-glucose conditions.
- Analysis of exosome production and miRNA content from INS-1 cells.
- Investigating the effect of exosomes on Müller cells, including oxidative stress and apoptosis induction.
- In vivo validation using high-fat diet and miR-15a knockout mouse models.
Main Results:
- Plasma miR-15a levels correlate with T2D severity.
- Pancreatic beta-cells secrete exosomes containing elevated miR-15a under high-glucose conditions.
- Exosomes from high-glucose treated beta-cells induce miR-15a overexpression in Müller cells, leading to oxidative stress and apoptosis via Akt3 targeting.
- In vivo studies support the role of miR-15a in T2D complications.
Conclusions:
- Circulating miR-15a, delivered via exosomes from pancreatic beta-cells, contributes to T2D pathogenesis.
- This study demonstrates a novel mechanism of remote cell-cell communication involving exosomal miRNAs in T2D.
- Exosomal miR-15a transfer induces oxidative stress and cell injury, highlighting its role in diabetes complications.
