New breakthroughs in understanding the genetic basis of glaucoma

A large international group of scientists jointly directed by Moorfields’ consultant Ananth Viswanathan has identified four new genetic variants linked to the risk of glaucoma – the leading cause of irreversible blindness in the world.

The study, recently published in Nature Genetics, examined 35,926 people and analysed their genomes to discover genetic markers for intraocular pressure (IOP). IOP, commonly measured by an ‘air puff’ test at an optician’s, is a major risk factor for the development and worsening of glaucoma and is the only treatable element of the disease.

One of the most significant findings was that variants in the ABCA1 gene, which help strengthen cell membranes by regulating cellular cholesterol and lipid metabolism, play a role in the determination of IOP. Last year, a group led by Mr Viswanathan discovered that variants in the ICA1 gene, also involved in lipid metabolism, are strongly related to IOP level.

Mr Viswanathan said: “The discoveries are significant because they improve our understanding of the risk of this serious disease and may lead to better treatments.”

The findings of two other studies on glaucoma were also published last week in Nature Genetics. These studies compared glaucoma patients to healthy control subjects to detect genetic differences. One of these studies, which Mr Viswanathan co-authored, also identified sequence variations of the ABCA1 gene as playing a role in the disease. This finding also contributed to the third published study, submitted by a group of scientists from Asian institutions and investigating the genetic basis of glaucoma in East Asians.

Mr Viswanathan  said: “These studies not only confirm the findings  of previous work, but the new finding of a consistent implication  of the ABCA1 gene in the determination of IOP and glaucoma, which  points to lipid metabolism as a key metabolic pathway in the disease and in the disease course.

“The work has also thrown light on some new associated risk factors. For example, in our study we have found support for the theory that the thickness of the cornea, the front window of the eye, might be independently related to IOP rather than merely biasing the measurements of IOP by interfering with the ‘air puff test’, as is often thought. This is because we found that variants in the FNDC3B gene, which we know is associated with corneal thickness, are involved in the determination of IOP even when the biasing effect of corneal thickness is taken into account.”

He added that the results of the studies also highlight why international research collaboration is invaluable. “By taking this ‘big data’ approach, we have found out more about the biology of the disease, new genomic areas and have been able to confirm the findings in different parts of the globe. These studies were undertaken in the EU, Australia, USA  and Asia, which gives them a very strong evidence base and also makes the best use of resources as the costs of these large scale studies are huge.”

Glaucoma is caused by damage to the optic nerve, often by a build up of fluid in the eyeball (raised intraocular pressure). Early diagnosis is vital, as the damage can often be averted before it causes serious problems. Spotting patients who are genetically more at risk would therefore be highly desirable.

According to the UN's World Health Organization (WHO), 4.5 million people around the world have become blind through glaucoma, with the disease accounting for around one in eight of cases of blindness.

Editors Notes

• Moorfields is one of the world’s leading eye hospitals, providing expertise in clinical care, research and education. We have provided excellence in eye care for more than 200 years and we continue to be at the forefront of new breakthroughs and developments.  We are an integral part of one of the UK’s first academic health science centres, UCL Partners, and also one of the new academic health science networks. We were one of the first NHS organisations to achieve foundation trust status in 2004. 

• We treat the entire range of eye diseases, from common complaints to rare conditions which require treatments not available anywhere else in the UK.
• We dealt with more than 470,000 patient attendances in 2013/14 across our 21 locations in and around London, enabling us to provide expert care closer to patients’ homes.

• Our specialist A&E dealt with almost 90,000 patient visits in the year 2013/14.

• With our academic partners at the UCL Institute of Ophthalmology, Moorfields is recognised as a leading centre of excellence in eye  and vision research. Together, we form one of the largest ophthalmic research sites in the world, with the largest patient population in Europe  or the USA. We publish more scientific papers than any other eye  and vision research site, and have an extensive joint research portfolio.