Genetic and Gender Factors Linked to Fuchs Endothelial Corneal Dystrophy in University College London Study
These findings could support gene therapies targeting CTG18.1 that are currently in development.
This article originally appeared on our sister site, Ophthalmology Times Europe®.
Figure. Slit-scanning in vivo confocal microscopy images of the corneal endothelium: A (left) demonstrates a healthy control cornea: Image of a normal corneal endothelium, showing a uniform hexagonal cell pattern with consistent cell density and no visible guttae or abnormalities (white solid arrowhead). B (right) shows FECD: Increased confluency of guttata, illustrating a more extensive presence of these structures. Images courtesy UCL/NIHR Moorfields Biomedical Research Centre.
Genetic and demographic factors, including gender, contribute to Fuchs Endothelial Corneal Dystrophy (FECD), according to research led by the University College London (UCL) Institute of Ophthalmology and supported by National Institute for Health and Care Research (NIHR) Moorfields Biomedical Research Centre. The large-scale study was published in JAMA Ophthalmology.
The study featured the largest cohort to date, with 894 patients with FECD included. Patients are more likely to develop FECD if they have an alteration in the TCF4 gene, according to a press release put out by the NIHR, Moorfields and UCL. Furthermore, a DNA sequence called CTG18.1, and the number of copies present in a patient’s genetic information, are linked to the severity of FECD.
Patients of European and South Asian descent showed high incidences of the CTG sequence repeat and were likely to have 50 or more copies of the CTG repeat in their DNA, the authors noted. In addition, FECD was more likely to be found in women, and this gender disparity was greater among patients who do not have the CTG18.1 expansion. This suggests that gender-specific factors may contribute to development of FECD, according to the authors.
“We are thrilled to share these findings, which represent a significant step forward in our understanding of FECD,” lead study investigator Alice Davidson, PhD, a professor of molecular genetics at the UCL Institute of Ophthalmology, said. “By uncovering the critical role of the CTG18.1 repeat expansion in the TCF4 gene, particularly its impact on disease risk and severity in the context of demographic factors, we are paving the way for more personalised approaches to treatment. Our study not only broadens our understanding of the genetic drivers of FECD across diverse populations but also underscores the importance of integrating genetic testing into clinical care.”
FECD is an inherited disorder, which, primarily affects the cornea and is a leading cause of age-related vision loss. In low-income countries, FECD is the most common reason for corneal transplants. This study suggests that further investigation should explore genetic aspects of FECD and how demographic factors may impact the disease pathology and treatment. These findings could support gene therapies targeting CTG18.1 that are currently in development.
