Liverpool Keratomics Study
Research type
Research Study
Full title
Genomic and Epigenomic studies in corneal disease: Investigating the DNA sequence, DNA methylation and gene expression changes in corneal ectasias and dystrophies.
IRAS ID
262037
Contact name
Louise F Porter
Contact email
Sponsor organisation
University of Liverpool
Clinicaltrials.gov Identifier
xx, xx
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Corneal ectasias and dystrophies are disorders that affect the cornea, the transparent window on the front of the eye. They represent common causes of visual loss in young adults. Keratoconus (KC) is the most common corneal ectasia and the leading indication for corneal transplantation.
To date, the causes of KC are not known, and surgical procedures (corneal cross-linking, corneal transplantation) are the main treatment options. Importantly, KC occurs mainly in patients with allergies, suggesting gene-environment interaction components. DNA methylation, a chemical modification to DNA, is a genetic factor affected by the environment which has not been studied to date.
We propose to analyse DNA methylation levels across the whole of the DNA in patients with KC and corneal dystrophies using a DNA methylation gene chip, and compare these levels to unaffected controls.
Because DNA methylation varies in different tissues, we need to source DNA from the cornea. Samples of corneal tissue will be obtained from patients having routine surgery and from deceased eye donors via our Liverpool Research Eye Bank (LREB). DNA methylation changes identified will be confirmed using a different technique (bisulphite pyrosequencing), to ensure consistency. We will also look at whether the genes that have different DNA methylation levels in the affected tissues express different amounts of gene product by measuring the RNA (the product of the gene) in the donated corneal tissues from patients. In selected cases with a strong family history of corneal disease the DNA sequence itself will be analysed by DNA sequencing.
The study will the first study to analyse DNA methylation in KC and corneal dystrophies. The discovery of genes with different methylation and expression levels in the disease will provide new drug targets to develop much needed non-surgical treatment options for patients, as DNA methylation can be altered therapeutically.REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
21/NW/0033
Date of REC Opinion
13 Apr 2021
REC opinion
Further Information Favourable Opinion