Early Transcriptomic and Pathologic Changes of Col8a2 Mutant Fuchs Endothelial Corneal Dystrophy.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Fuchs endothelial corneal dystrophy (FECD) is a progressive eye disease affecting the corneal endothelium.
• Understanding early molecular changes is crucial for developing timely interventions.
• The Col8a2Q455K/Q455K mutant mouse model offers a platform to study FECD pathogenesis.

Purpose of the Study:

• To characterize early transcriptomic and pathologic alterations in FECD.
• To utilize the Col8a2Q455K/Q455K mutant mouse model for FECD research.
• To identify potential early biomarkers for FECD.

Main Methods:

• Divided mutant mice into early (≤2 months) and late (≥8 months) stages based on corneal endothelial changes.
• Evaluated corneal endothelium using slit-lamp microscopy, OCT, and confocal microscopy.
• Performed transcriptomic analysis on corneal endothelial cells and validated findings with qPCR and immunofluorescence.

Main Results:

• Mutant mice showed no abnormalities before 2 months; morphological changes appeared at 4 months with edema.
• Transcriptomic analysis revealed 221 upregulated and 55 downregulated genes in early-stage mutants compared to wild-type.
• Upregulated genes were enriched in ECM remodeling, ER stress, and immune response pathways, validated by qPCR and immunofluorescence prior to morphological changes.

Conclusions:

• Col8a2Q455K/Q455K mutant mice exhibit aberrant ECM remodeling, ER stress, and immune responses before observable FECD pathology.
• This study provides the first in vivo evidence of potential early biomarkers for FECD.
• Findings suggest potential targets for early therapeutic interventions in FECD.