Integrated microRNA and mRNA Profiling in the Corneal Endothelium of Fuchs Endothelial Corneal Dystrophy
4 affiliations
- 1Medical Genomics Laboratory, Lopukhin Federal Research and Clinical Center of Physical, Chemical Medicine of the Federal Medical Biological Agency, Moscow 119435, Russia
- 2Federal State Budgetary Educational Institution, Higher Education “Russian University of Medicine”, The Ministry of Health of the Russian Federation, Moscow 127006, Russia
- 3The Jules Stein Eye Institute, University of California at Los Angeles, 200 Stein Plaza, Los Angeles, CA 90095, USA
- 4Department of Anterior Segment Transplant and Optical Reconstructive Surgery, S. Fyodorov Eye Microsurgery Complex Federal State Institution, Moscow 127486, Russia
Abstract
MicroRNAs (miRNAs) are endogenous non-coding RNAs that post-transcriptionally modulate gene expression, playing roles in both development and disease pathogenesis. This study specifically investigates the differential miRNA expression in human FECD endothelium compared to healthy controls. By integrating this miRNAome profile with our existing transcriptomic background, we aimed to identify candidate miRNA–target gene regulatory relationships potentially relevant to FECD. NanoString nCounter miRNA profiling was performed on corneal endothelium from FECD patients and controls. Differential expression analysis was conducted, followed by correlation of miRNAs with transcriptomic data from matched samples. Functional enrichment was performed for negatively correlated miRNA–mRNA pairs to identify pathways relevant to FECD pathogenesis. We found 98 differentially expressed miRNAs between FECD and controls. Correlation analysis revealed negatively correlated candidate miRNA–target gene pairs, highlighting potential regulatory interactions. Enrichment analysis of target genes implicated PI3K-AKT, TNF, AGE-RAGE, and focal adhesion pathways as part of FECD molecular alterations. Several dysregulated miRNAs (e.g., miR-302 and miR-630) were associated with processes such as extracellular matrix remodeling, apoptosis, and inflammatory signaling, consistent with key pathogenic features of FECD. This exploratory study provides new insights into the pathogenesis of FECD by integrating miRNA profiling with a transcriptomic background. This combined analysis highlights candidate miRNA–target associations identified within the FECD group and places them into potentially regulatory pathways relevant to endothelial degeneration. The observed miR-29 expression trends are hypothesis-generating; however, the miR-29 family did not meet the prespecified FDR threshold and was not retained in the final correlation network, precluding confirmation of its contribution to ECM remodeling in our cohort. In parallel, comparison with earlier array-based studies revealed inconsistencies that may partly reflect differences in platforms and cohorts; these discrepancies warrant further investigation in independent cohorts. Finally, the analysis of mirtronic host genes uncovered unstable correlations, suggesting that array-based measurements alone are insufficient for reliable miRNA quantification. Together, these findings refine our understanding of FECD-related networks, resolve some earlier contradictions, and open directions for more robust validation and therapeutic exploration.
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BibTeX
@article{ryazantsev2026integrated,
title = {{Integrated microRNA and mRNA Profiling in the Corneal Endothelium of Fuchs Endothelial Corneal Dystrophy}},
author = {Dmitriy Ryazantsev and Elena Sharova and Denis Gudkov and Anastasia Voronkova and Boris Malyugin and Olga Antonova and Alexandra Belodedova and Liubov Skorodumova},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110044},
url = {https://www.mdpi.com/1422-0067/27/21/10044},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated microRNA and mRNA Profiling in the Corneal Endothelium of Fuchs Endothelial Corneal Dystrophy
AU - Dmitriy Ryazantsev
AU - Elena Sharova
AU - Denis Gudkov
AU - Anastasia Voronkova
AU - Boris Malyugin
AU - Olga Antonova
AU - Alexandra Belodedova
AU - Liubov Skorodumova
PY - 2026
DA - 2026/11/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110044
UR - https://www.mdpi.com/1422-0067/27/21/10044
AB - MicroRNAs (miRNAs) are endogenous non-coding RNAs that post-transcriptionally modulate gene expression, playing roles in both development and disease pathogenesis. This study specifically investigates the differential miRNA expression in human FECD endothelium compared to healthy controls. By integrating this miRNAome profile with our existing transcriptomic background, we aimed to identify candidate miRNA–target gene regulatory relationships potentially relevant to FECD. NanoString nCounter miRNA profiling was performed on corneal endothelium from FECD patients and controls. Differential expression analysis was conducted, followed by correlation of miRNAs with transcriptomic data from matched samples. Functional enrichment was performed for negatively correlated miRNA–mRNA pairs to identify pathways relevant to FECD pathogenesis. We found 98 differentially expressed miRNAs between FECD and controls. Correlation analysis revealed negatively correlated candidate miRNA–target gene pairs, highlighting potential regulatory interactions. Enrichment analysis of target genes implicated PI3K-AKT, TNF, AGE-RAGE, and focal adhesion pathways as part of FECD molecular alterations. Several dysregulated miRNAs (e.g., miR-302 and miR-630) were associated with processes such as extracellular matrix remodeling, apoptosis, and inflammatory signaling, consistent with key pathogenic features of FECD. This exploratory study provides new insights into the pathogenesis of FECD by integrating miRNA profiling with a transcriptomic background. This combined analysis highlights candidate miRNA–target associations identified within the FECD group and places them into potentially regulatory pathways relevant to endothelial degeneration. The observed miR-29 expression trends are hypothesis-generating; however, the miR-29 family did not meet the prespecified FDR threshold and was not retained in the final correlation network, precluding confirmation of its contribution to ECM remodeling in our cohort. In parallel, comparison with earlier array-based studies revealed inconsistencies that may partly reflect differences in platforms and cohorts; these discrepancies warrant further investigation in independent cohorts. Finally, the analysis of mirtronic host genes uncovered unstable correlations, suggesting that array-based measurements alone are insufficient for reliable miRNA quantification. Together, these findings refine our understanding of FECD-related networks, resolve some earlier contradictions, and open directions for more robust validation and therapeutic exploration.
SN - 1422-0067
ER -