Heterozygous Tcf4 Deficiency Mitigates Fuchs Endothelial Corneal Dystrophy Progression in a Mouse Model

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(4), С. 19 - 19

Опубликована: Апрель 8, 2025

The purpose of this study was to use Col8a2Q455K/Q455K mice, an established Fuchs endothelial corneal dystrophy (FECD) model, investigate whether heterozygous knockout Tcf4 expression could ameliorate the progression FECD. mice were generated using CRISPR/Cas9-mediated deletion exons 2 and 3. These crossed with obtain Col8a2Q455K/Q455K/Tcf4± mice. Differential gene profiles in cells then examined RNA sequencing. Guttae formation cell density assessed contact specular microscopy. Expression extracellular matrix (ECM) components evaluated by qPCR immunofluorescence analysis. RNA-Seq analysis revealed 1053 differentially expressed genes between significant enrichment ion channel-related pathways downregulation TNF-associated signaling pathways. Contact microscopy 28-week-old demonstrated that guttae significantly lower than (0.71 ± 0.77% vs. 1.87 1.43%, P < 0.001), whereas higher (1819 170 1521 292 cells/mm², 0.001). ECM components-particularly fibronectin type I collagen, which are major constituents guttae-were decreased Heterozygous suppressed FECD phenotype, including loss, mouse model. findings provide vivo support for TCF4 as a potential therapeutic target treatment.

Язык: Английский

---

The application and progression of CRISPR/Cas9 technology in ophthalmological diseases

Eye, Год журнала: 2022, Номер 37(4), С. 607 - 617

Опубликована: Авг. 1, 2022

Язык: Английский

---

Comparison of Scheimpflug and Anterior Segment Optical Coherence Tomography Imaging Parameters for Japanese Patients With Fuchs Endothelial Corneal Dystrophy With and Without TCF4 Repeat Expansions

Cornea, Год журнала: 2024, Номер 43(7), С. 805 - 811

Опубликована: Фев. 1, 2024

Purpose: The aim of this study was to investigate the association between cytosine–thymine–guanine trinucleotide repeat (TNR) expansion in TCF4 and clinical phenotypes corneal densitometry or anterior segment morphology Fuchs endothelial dystrophy. Methods: This retrospective cross-sectional included 150 eyes from 75 Japanese consecutive patients with Cytosine–thymine–guanine leukocyte-derived genomic DNA analyzed through fragment analysis using polymerase chain reaction triplet primed reaction. Scheimpflug-based optical coherence tomography were applied. Corneal densitometry, parameters compared without TNR 50 more (expansion nonexpansion groups, respectively) a mixed model. Results: average age 66.8 ± 13.0 years, modified Krachmer grading scale 1, 2, 3, 4, 5, 6 for 7, 32, 28, 51, 6, 18 eyes, respectively. Sixteen (21%) exhibited ≥50 expansion. No significant differences sex, age, history keratoplasty, grade, either diameter depth observed 2 groups. morphology, including chamber angle width parameters, univariate model, except central thickness ( P = 0.047). However, according multivariate not significantly associated 0.27). Conclusions: found having dystrophy

Язык: Английский

---

Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year

Cornea, Год журнала: 2024, Номер 43(10), С. 1207 - 1215

Опубликована: Июль 9, 2024

Purpose: To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to extent triplet repetition in transcription factor 4 (TCF4) gene. Methods: A prospective study with a 1-year follow-up was conducted. total 104 patients (160 eyes) FECD an equivalent number age- sex-matched control subjects without were included. At inclusion, corneas graded using modified Krachmer grade (KG) genotyped for trinucleotide repeats (TNRs) TCF4 gene by short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, Function Corneal Health Status visual disability instrument measured on 2 visits at intervals. Results: KGs ranged from 6, 46% eyes had grades 4. 71% harbored TNR expansion (>40) versus 13% ( P < 0.001). Severity inclusion higher presence when considering independently (mean ±SD, 4.08 ± 1.42) 4.66 1.27 = 0.024). In year, ETDRS score significantly decreased −2.97 (95% confidence interval −4.69 −1.26, 0.001) glare −4.25 −6.22 −2.27, 10 −5 ). There no relationship between rate decline or KG. Central thickness scores did not vary. Conclusions: It possible measure subtle progression period as year. We find speed deterioration This work should facilitate design future trials FECD.

Язык: Английский

---

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

---