Genetic study reveals hidden pieces of eye disease puzzle – sciencedaily


Scientists have taken a big step forward in their search for the origin of a progressive eye disease that causes vision loss and can lead to a cornea transplant.

New keratoconus study by an international team of researchers, including a group from Leeds University led by Chris Inglehearn, professor of molecular ophthalmology at the Faculty of Medicine, has detected DNA variations for the first time that could provide clues as to how the disease is developing.

Keratoconus causes the cornea, which is “the clear outer layer” at the front of the eye, to thin and swell outward into a cone shape over time, resulting in blurred vision. and sometimes blindness. It usually appears in adulthood, often with lifelong consequences, and affects 1 in 375 people on average, although in some populations the figure is much higher.

It’s more common in people with an affected relative, leading scientists to believe there could be a genetic link.

Glasses or contact lenses can be used to correct vision in the early stages. The only treatment is “corneal crosslinking,” a procedure where targeted UV light is used to strengthen corneal tissue. In very advanced cases, a cornea transplant may be necessary.

Professor Inglehearn said: “This multinational, multi-center study gives us the first real information on the cause of this potentially blinding disease and paves the way for genetic testing in those at risk. “

The team, led by Alison Hardcastle, professor of molecular genetics at the UCL Institute of Ophthalmology, and Dr Pirro Hysi at King’s College London, and comprising researchers from the UK, USA, Czech Republic , from Australia, the Netherlands, Austria and Singapore, compared the complete genetic codes of 4,669 people with keratoconus to that of 116,547 people without conditions.

The team identified short sequences of DNA that were significantly altered in the genomes of people with keratoconus, offering clues to its development.

The results indicate that people with keratoconus tend to have defective collagen networks in their corneas, and that there may be abnormalities in the programming of cells that affect their development. These promising ideas were not possible in previous studies due to insufficient sample sizes.

Future work will now aim to understand the precise effects of these DNA variations on corneal biology and to identify the mechanism by which keratoconus then develops. It will also be crucial to identify any remaining genetic variations among keratoconus patients that were not detected in this study.

The work has brought science closer to earlier diagnosis and potentially even new therapeutic targets, offering hope to current and future keratoconus patients.

The study, A Genome-Wide Multiethnic Association Study Involves Collagen Matrix Integrity and Cell Differentiation Pathways in Keratoconus, was funded by Moorfields Eye Charity and is published in Communications biology today.

Dr Hysi said: “The results of this work will allow us to diagnose keratoconus even before it manifests; this is great news because early intervention can avoid blinding consequences. “

Professor Hardcastle said: “This study represents a substantial advance in our understanding of keratoconus. We can now use this new knowledge as a basis to develop a genetic test to identify individuals at risk for keratoconus, at a stage where vision can be preserved, and to develop more effective treatments in the future. “

Professor Stephen Tuft, Moorfields Eye Hospital, said: “If we can find ways to identify keratoconus early, corneal collagen crosslinking can prevent disease progression in the vast majority of cases.

“We would like to thank the thousands of people who attend our cornea clinic at Moorfields Eye Hospital and who donated a DNA sample, without whom this important study would not have been possible.”

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