Dysregulation of Transient Receptor Potential Cation Channels and Epithelial-to-Mesenchymal Transition-Related Genes in Fuchs Endothelial Corneal Dystrophy: A Bioinformatics Approach

Gaikwad KB, BV H, Narayanan J, Padmanabhan P, Tourtas T, Schlötzer-Schrehardt U, Kruse F, Yuasa T, Koizumi N, Okumura N, Jolly MK, Elchuri SV, Sharma J (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cornea Lippincott, Williams & Wilkins

Book Volume: Publish Ahead of Print

Article Number: 10.1097/ICO.0000000000004099

DOI: 10.1097/ICO.0000000000004099

Abstract

Purpose: – To investigate dysregulated ion channels and epithelial-to-mesenchymal transition (EMT) genes in Fuchs endothelial corneal dystrophy (FECD) and to identify potential drugs interacting with dysregulated ion channels.Methods: – Five RNA-sequencing datasets from patients with FECD were analyzed with DESeq2 to identify differentially expressed genes. Dysregulated ion channels and EMT-related genes underwent enrichment analysis and EMT scoring via the KS method. Coexpression patterns were identified using weighted gene coexpression network analysis. A pathway map highlighted altered cellular processes in FECD, and potential drugs were identified using the Drug–Gene Interaction Database. Molecular docking assessed binding of drugs with TRPV4 and TRPM8. Selected gene expression changes were validated by quantitative real-time polymerase chain reaction.Results: – Analysis identified 12, 550 differentially expressed genes, including 229 ion channels (157 up-regulated, 72 down-regulated) and 502 EMT-related genes (304 up-regulated, 198 down-regulated). Functional enrichment revealed disrupted biological processes including interleukin-1 production and extracellular matrix organization organization. Coexpression analysis uncovered 2 modules linked to apoptosis and senescence. Up-regulated transient receptor potential cation (TRP) cation channels correlated with elevated senescence; altered NFKBIA, NFKB1, and TNFSF10 expression with endothelial apoptosis. We identified 1052 drugs targeting 133 dysregulated ion channels and performed docking analysis for TRP channels. Experimental validation confirmed altered expression of TRPV1, CDKN2A, and KRT7.Conclusions: – Dysregulated TRP cation channels contribute to cellular senescence and peripheral sensitization in FECD, whereas altered apoptotic regulators drive corneal endothelial cell death. Most likely, these pathways represent potential targets for treatment of patients with FECD.

Authors with CRIS profile

Theofilos Tourtas Lehrstuhl für Augenheilkunde Ursula Schlötzer-Schrehardt Department of Ophthalmology Friedrich Kruse Lehrstuhl für Augenheilkunde

Involved external institutions

Indian Institute of Science (IISc) IN India (IN) Sankara Nethralaya IN India (IN) Doshisha University / 同志社大学 JP Japan (JP) Manipal University / Manipal Academy of Higher Education (MAHE) IN India (IN)

How to cite

APA:

Gaikwad, K.B., BV, H., Narayanan, J., Padmanabhan, P., Tourtas, T., Schlötzer-Schrehardt, U.,... Sharma, J. (2026). Dysregulation of Transient Receptor Potential Cation Channels and Epithelial-to-Mesenchymal Transition-Related Genes in Fuchs Endothelial Corneal Dystrophy: A Bioinformatics Approach. Cornea, Publish Ahead of Print. https://doi.org/10.1097/ICO.0000000000004099

MLA:

Gaikwad, Kiran Bharat, et al. "Dysregulation of Transient Receptor Potential Cation Channels and Epithelial-to-Mesenchymal Transition-Related Genes in Fuchs Endothelial Corneal Dystrophy: A Bioinformatics Approach." Cornea Publish Ahead of Print (2026).

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