ArticleInvestigative ophthalmology & visual science2025
The TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- TCF4 trinucleotide repeat expansion drives distinct proteomic signatures in Fuchs endothelial corneal dystrophy.Scientific reports · 2026Article
- Transcription factor 4 and Fuchs' endothelial corneal dystrophy (FECD) association: Perspectives for novel targeted therapeutics.Eye (London, England) · 2025Article
- Treatment Outcomes of Upside-Down Descemet Membrane Endothelial Keratoplasty.Journal of clinical medicine · 2025Article
- Corneal Endothelium Regeneration with Decellularized Porcine Corneal Extracellular Matrix Scaffolds.Tissue engineering and regenerative medicine · 2025Article
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Authors and funding
19 authors.
Funding
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Abstract
Purpose: Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disorder characterized by excessive extracellular matrix (ECM) accumulation and corneal endothelial cell death. CTG trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene represents the most significant genetic risk factor. This study aimed to elucidate the role of TCF4 in FECD pathogenesis through comprehensive proteomic analysis. Methods: Corneal endothelial cells isolated from patients with FECD harboring TCF4 trinucleotide repeat expansion were immortalized to establish an FECD cell model (iFECD). CRISPR/Cas9-mediated genome editing was employed to generate TCF4-knockout iFECD cells. Whole-cell proteome analysis was performed using liquid chromatography-mass spectrometry, followed by pathway enrichment analysis of differentially expressed proteins (DEPs). The effects of TCF4 deletion on TGF-β-mediated protein aggregation and cell death were evaluated using Western blot analysis, flow cytometry, and aggresome detection assays. Results: Proteomic analysis identified 88 DEPs among 6510 detected proteins. Pathway analysis revealed significant enrichment in ECM-associated pathways, oxidative stress responses, and cellular motility. TCF4 deletion attenuated TGF-β-induced cell death in iFECD cells. Concordantly, Western blot analysis demonstrated that TCF4 deletion suppressed TGF-β2-mediated cleavage of caspase-3 and poly (ADP-ribose) polymerase. Flow cytometric analysis of Annexin V-positive cells confirmed reduced apoptosis in TCF4-deleted cells following TGF-β2 treatment. Additionally, aggresome detection assays revealed that TCF4 deletion diminished TGF-β2-induced protein aggregation. Conclusions: This study demonstrates a crucial role for TCF4 in FECD pathogenesis, particularly in ECM regulation and protein aggregation-induced cell death.
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