How “Omics” Studies Contribute to a Better Understanding of Fuchs’ Endothelial Corneal Dystrophy

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 135 - 135

Опубликована: Фев. 20, 2025

Fuchs’ endothelial corneal dystrophy (FECD) is a progressive eye disease characterized by accelerated loss of cells and the development focal excrescence (guttae) on Descemet’s membrane, resulting in cornea opacity vision deterioration. The FECD assumed to be due interplay between genetic environmental factor risks, causing abnormal extracellular-matrix organization, increased oxidative stress, apoptosis unfolded protein response. However, molecular knowledge limited. genome-wide platforms bioinformatics approaches has enabled us identify numerous loci that are associated with FECD. In this review, we gathered studies (n = 31) sorted them according genomics 9), epigenomics 3), transcriptomics 15), proteomics 3) metabolomics 1) levels characterize progress understanding We also extracted validated differentially expressed/spliced genes proteins identified through comparisons case control groups. addition, highlighted from each omics layer were combined comparison similar study groups original for downstream gene-set enrichment analysis, which provided most significant biological pathways related organization. future, multiomics needed increase sample size statistical power strong candidate functional animal models cell lines better

Язык: Английский

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Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity

JAMA Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Importance Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. Objective To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. Design, Setting, Participants This retrospective cohort study recruited 894 individuals with Moorfields Eye Hospital (London) General University (Prague) from September 2009 July 2023. Ancestry was inferred genome-wide single nucleotide polymorphism array data. CTG18.1 status determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (≥50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases exome sequenced. Main Outcomes Measures Association variants FECD-associated genes, data, keratoplasty. Results Within total (n = 894), 77.3% patients Exp+. Most European (668 829 [80.6%]) South Asian (14 22 [63.6%]) The percentage female higher (151 [74.4%]) Exp- compared Exp+ (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P < .001). median (IQR) Exp + (68.2 years [63.2-73.6]) older than (61.3 [52.6-70.4]; 6.5 years; 3.4-9.7; length largest allele within group inversely correlated (β, −0.087; −0.162 −0.012; .02). ratio biallelic monoallelic (1:14) an unaffected control (1:94; .001), indicating that 2 associated increased disease penetrance 1 expansion. Potentially (minor frequency, <0.01; combined annotation dependent depletion, >15) only identified genes 13 (10.1%). Conclusions Relevance In this multicenter among FECD, expansions present most patients, while zygosity modifications severity penetrance. Known disease-associated accounted for minority cases, unknown risk factors rest subgroup. These may have implications future therapy development.

Язык: Английский

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Genotype–Phenotype Correlations in Corneal Dystrophies: Advances in Molecular Genetics and Therapeutic Insights

Clinical and Experimental Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

ABSTRACT Corneal dystrophies are a group of predominantly rare inherited disorders. They by definition bilateral, relatively symmetrical, and without systemic involvement, affecting corneal transparency and/or refraction. Traditional classification is based on slit‐lamp appearance, affected layer histological features. Molecular genetics has provided ultimate proof for the existence distinct discarded duplicates in their terminology. Currently, there at least 16 genes with identified pathogenic variants implicated dystrophies. Herein, we summarise contemporary knowledge genotype–phenotype correlations dystrophies, including critical review some reported variants, along understanding underlying dystrophic process; essential development targeted therapies.

Язык: Английский

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Preclinical Models for Studying Fuchs Endothelial Corneal Dystrophy

Cells, Год журнала: 2025, Номер 14(7), С. 505 - 505

Опубликована: Март 28, 2025

Fuchs Endothelial Corneal Dystrophy (FECD) is a corneal endothelial disease that causes microenvironment alterations and cell loss, which leads to vision impairment. It has high global prevalence, especially in elderly populations. FECD also one of the leading indications transplantation globally. Currently, there no clearly defined canonical pathway for this disease, it been proposed combinatorial effects genetic mutations exogenous factors cause FECD. Clinical studies observations have provided valuable knowledge understanding FECD, while preclinical are essential gaining insights into progression mechanisms development testing regenerative medicine therapies. In review, we first introduce molecular pathologies Notably, discuss impact abnormal extracellular matrix deposition (guttata), endothelial-to-mesenchymal transition, senescence, oxidative stress on pathology etiology We review summarize vitro models, ex vivo tissues, animal models used study The benefits challenges each model discussed.

Язык: Английский

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Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping

EBioMedicine, Год журнала: 2024, Номер 108, С. 105328 - 105328

Опубликована: Сен. 14, 2024

Язык: Английский

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