Exfoliation syndrome (XFS): Discovered gene allows a peek into the future on eye disease

An international research collaboration led by Singaporean researchers have led to the discovery of a mutated gene that renders people highly susceptible to a severe eye disorder called Exfoliation Syndrome (XFS). The study involved 8,400 patients from 17 countries and was reported in the prestigious scientific journal, Nature Genetics.

The scientists found that Singaporean Chinese with the mutation are 40 to 56 percent more likely to develop XFS some time in their lives compared to Singaporean Chinese without the mutation. They also noted that Singaporean Indians with the mutation are between 19 to 25 percent more likely to develop XFS some time in their lives compared against Singaporean Indians without the mutation. This figure is in stark contrast to the global average of 16 to 25 per cent of similar individuals likely to develop XFS. The study is led by researchers from A*STAR's Genome Institute of Singapore (GIS) and the Singapore Eye Research Institute (SERI).

XFS usually develops in people above the age of 60 years old and is characterised by the body's inability to remove abnormal protein deposits from inside the eye. The accumulation of these protein deposits clogs the eye's drainage mechanism that results in a build-up of fluid and pressure in the eye in a condition called Glaucoma. If left untreated, a person with glaucoma can become permanently blind.

The gene believed to be responsible for XFS is called CACNA1A. The scientists found that CACNA1A affects the body's calcium transport channels, which are important for many vital biological functions. Those who carry the CACNA1A gene have faulty calcium transport channels that hinder normal bodily functions, such as the eye's ability to efficiently remove abnormal protein deposits.

A*STAR's Dr Khor Chiea Chuen from GIS said, "Glaucoma is one of the most common eye diseases in Singapore and around the world. With this knowledge, we can now concentrate our efforts to develop therapeutic solutions to address and normalise the calcium signalling function in order to reduce the risk of XFS and the development of glaucoma."

SERI Executive Director and Senior Consultant and Head of Glaucoma Service, Singapore National Eye Centre, Prof Aung Tin said, "This is an exciting discovery as the pathway we have found could be a target for new therapies and medications to prevent or treat this type of glaucoma."

"On a personal level," added Prof Aung, "the project was extremely stimulating and interesting as we were working with more than 90 collaborating sites from 17 different countries in Asia, Europe, Australia, Africa, North America and South America. It was a huge honour for us in Singapore to be coordinating and leading this global study of such scale and impact."

Prof Robert Ritch, Shelley and Steven Einhorn Distinguished Chair, Professor of Ophthalmology and Surgeon Director and Chief (Glaucoma Services) at The New York Eye and Ear Infirmary said, "This new gene may not only explain some of the manifestations of Exfoliation Syndrome, but may also help us explain why associated systemic diseases occur in conjunction with it. This discovery opens doors to further elucidation, understanding, and perhaps new treatments for Exfoliation Syndrome." Prof Ritch is also the founder, medical director and chairman of the Scientific Advisory Board at The Glaucoma Foundation.

"This is a very important study showing association of a novel DNA variant with disease risk in populations throughout the world," added Janey L. Wiggs, who holds the post as the Paul Austin Chandler Associate Professor of Ophthalmology at the Harvard Medical School. Prof Wiggs jointly supervised the project.

"Exfoliation Syndrome is a debilitating disorder affecting many people in the world. The study is highly relevant to local as well as some foreign populations. The next step after this study is to capture the value from this new knowledge and turn it into health outcomes, such as to develop a genetic test to screen for XFS and new treatments for individuals carrying the CACNA1A gene," said Prof Ng Huck Hui, Executive Director, GIS.