ArticleInvestigative ophthalmology & visual science2019
Quantitative Studies of Muscleblind Proteins and Their Interaction With TCF4 RNA Foci Support Involvement in the Mechanism of Fuchs' Dystrophy.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 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
- Corneal Endothelial Progenitors for Ocular Regeneration: Translating Discovery into Clinical Therapies.International journal of molecular sciences · 2026Review
- The TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- CTG18.1 expansion in transcription factor 4 (TCF4) in corneal graft failure: preliminary study.Cell and tissue banking · 2024Article
- Targeting the ExpandedACS omega · 2023Article
- RNA-Seq-based transcriptome analysis of corneal endothelial cells derived from patients with Fuchs endothelial corneal dystrophy.Scientific reports · 2023Article
- The TCF4 Trinucleotide Repeat Expansion of Fuchs' Endothelial Corneal Dystrophy: Implications for the Anterior Segment of the Eye.Investigative ophthalmology & visual science · 2023Article
- Update on the genetics of corneal endothelial dystrophies.Indian journal of ophthalmology · 2022Review
- ArcRNAs and the formation of nuclear bodies.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins?Frontiers in genetics · 2022Review
- Expression and Function of ZEB1 in the Cornea.Cells · 2021Review
- TCF4-mediated Fuchs endothelial corneal dystrophy: Insights into a common trinucleotide repeat-associated disease.Progress in retinal and eye research · 2021Review
- Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis.Progress in retinal and eye research · 2021Review
- The Fuchs corneal dystrophy-associated CTG repeat expansion in the TCF4 gene affects transcription from its alternative promoters.Scientific reports · 2020Article
- Trinucleotide Repeat-Targeting dCas9 as a Therapeutic Strategy for Fuchs' Endothelial Corneal Dystrophy.Translational vision science & technology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: Fuchs' endothelial corneal dystrophy (FECD) is a major cause of vision loss and the most common nucleotide repeat disorder, affecting 4% of United States population greater than 40 years of age. Seventy percent of FECD cases are due to an intronic CTG expansion within the TCF4 gene, resulting in accumulation of CUG repeat RNA nuclear foci in corneal endothelium. Each endothelial cell has approximately two sense foci, and each focus is a single RNA molecule. This study aimed to obtain a better understanding of how rare repeat RNA species lead to disease. Methods: We quantitatively examined muscleblind-like (MBNL) proteins and their interaction with foci in both patient-derived corneal endothelial cell lines and human corneal endothelial tissue. Results: Using fluorescent in situ hybridization and immunofluorescence, we found that depletion of both MBNL1 and MBNL2 reduces nuclear RNA foci formed by the repeat, suggesting that both are necessary for foci. Quantitative studies of RNA and protein copy number revealed MBNLs to be abundant in the total cellular pool in endothelial cell lines but are much lower in human corneal endothelial tissue. Studies using human tissue nuclear and cytoplasmic fractions indicate that most MBNL proteins are localized to the cytoplasm. Conclusions: The low levels of MBNL1/2 in corneal tissue, in combination with the small fraction of protein in the nucleus, may make corneal endothelial cells especially susceptible to sequestration of MBNL1/2 by CUG repeat RNA. These observations may explain how a limited number of RNA molecules can cause widespread alteration of splicing and late-onset degenerative FECD.
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Registered trials
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