ArticleHuman molecular genetics2018
Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Systematic review of SLC4A11, ZEB1, LOXHD1, and AGBL1 variants in the development of Fuchs' endothelial corneal dystrophy.Frontiers in medicine · 2023Pooled it
- Tcf4 CTG Repeat Expansion Induces RNA Toxicity and MBNL-Associated Splicing Dysregulation in a Mouse Model of Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- Exploring the histopathological signature of repeat-mediated Fuchs endothelial corneal dystrophy.Acta ophthalmologica · 2026Article
- Advancements in CRISPR-based therapies for ocular pathologies: from disease mechanisms to intervention strategies.Theranostics · 2026Review
- Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.Molecular diagnosis & therapy · 2025Article
- Nuclear Argonaute:miRNA complexes recognize target sequences within chromatin-associated RNA and silence gene expression.Nucleic acids research · 2025Article
- Review
- The TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2025Article
- Endoplasmic Reticulum-Mitochondria Crosstalk in Fuchs Endothelial Corneal Dystrophy: Current Status and Future Prospects.International journal of molecular sciences · 2025Review
- Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.EBioMedicine · 2024Article
- CTG18.1 expansion in transcription factor 4 (TCF4) in corneal graft failure: preliminary study.Cell and tissue banking · 2024Article
- Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.PLoS genetics · 2024Article
- Expression and Impact of Fibronectin, Tenascin-C, Osteopontin, and Type XIV Collagen in Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2024Article
- The Role of Rho Kinase Inhibitors in Corneal Diseases.Drug design, development and therapy · 2024Review
- Targeting the ExpandedACS omega · 2023Article
- The TCF4 Trinucleotide Repeat Expansion of Fuchs' Endothelial Corneal Dystrophy: Implications for the Anterior Segment of the Eye.Investigative ophthalmology & visual science · 2023Article
- Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs' Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion.Ophthalmology science · 2023Article
- DNA methylation changes and increased mRNA expression of coagulation proteins, factor V and thrombomodulin in Fuchs endothelial corneal dystrophy.Cellular and molecular life sciences : CMLS · 2023Article
- The soil and the seed: The relationship between Descemet's membrane and the corneal endothelium.Experimental eye research · 2023Review
- Update on the genetics of corneal endothelial dystrophies.Indian journal of ophthalmology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.