Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy

• Published in: Experimental eye research 2023-06, Vol.231, p.109499-109499, Article 109499
• Main Authors: Ashraf, Shazia, Deshpande, Neha, Vasanth, Shivakumar, Melangath, Geetha, Wong, Raymond J., Zhao, Yan, Price, Marianne O., Price, Francis W., Jurkunas, Ula V.
• Format: Article
• Language: English
• Subjects: Animals; CTG repeat Expansion; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA repair; DNA Repair - genetics; DNA, Mitochondrial - genetics; Endothelium, Corneal - metabolism; Fuchs endothelial corneal dystrophy; Fuchs' Endothelial Dystrophy - genetics; Fuchs' Endothelial Dystrophy - metabolism; Genetic Predisposition to Disease; Humans; Mice; Mitochondrial DNA damage; Oxidative stress; TCF4
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2023.109499

Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (