Scientists pinpoint 3 new genes linked to the risk of primary open-angle glaucoma

An international team of researchers has discovered 3 new inherited risks for the most common type of glaucoma. Variations in the genes known as TXNRD2, ATXN2 and FOXC1 are linked to primary open angle glaucoma (POAG) and give us new targets for screening, prevention and treatment. We part-funded the study, published this week in Nature Genetics.

Glaucoma is a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common type. It involves slow sight loss due to damage and eventual death of the nerve cells that make up the optic nerve (the connection between eye and brain). This damage is usually caused by high pressure fluid in the eye, as small channels in the eye’s drainage system become blocked over time.

The current research was an overall analysis of data from 8 independent studies from the USA, 4 from Europe, 1 from Australia and 1 Singaporean Chinese study. In all, data from over 7,000 people with glaucoma and 42,000 controls (who didn’t have glaucoma) were included. They were mostly all white European.

Links to multiple conditions

Results link the gene FOXC1 for the first time to common glaucoma that starts as an adult. We already know that changes near this gene can mean that the front of the eye does not develop normally (a condition called ‘anterior segment dysgenesis’) or can bring on a type of glaucoma that begins earlier in life. FOXC1 also plays a part in controlling how cells detox and repair themselves from everyday wear and tear.

Neither of the genes ATXN2 nor TXNRD2 has been linked to any of the features of glaucoma before. But ATXN2 may be involved in nerve cell damage.

We know that certain faults in ATXN2 cause a movement disorder that comes together with optic nerve wasting (called spinocerebellar ataxia type 2 with optic atrophy). They can also be part of the cause of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease or Charcot disease.

TXNRD2 produces a protein that’s needed for the power-house battery compartments inside cells (mitochondria) to work properly. It’s the first mitochondrial protein to be linked to glaucoma.

Early Career Investigator Award

Dr Pirro Hysi is a genetic epidemiologist at King’s College London, who took part in the study with funds from a Fight for Sight Early Career Investigator Award. He said: “Our results suggest new pathways in eye development, neuro-degeneration and mitochondrial dysfunction that may contribute to the risk of developing glaucoma. Targeting these pathways could lead to effective treatment and perhaps strategies for early detection and prevention of this common form of glaucoma.” Read more about Dr Hysi’s work.

Dr Dolores M Conroy is Director of Research at Fight for Sight. She said: “Genome-wide association studies such as this one are really important for driving research forward in a direction that’s important to patients and people affected by sight loss.

We know from the Sight Loss and Vision Priority Setting Partnership that people want to know how glaucoma can be prevented and also who is at higher risk. Understanding the genetic causes of glaucoma is a significant step towards both.”

Patient benefit

Professor Sir Peng Tee Khaw, Director of the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology (the “NIHR Moorfields BRC”) commented, “This important research will help investigators and clinicians to develop future diagnostic tests and treatments to benefit patients. We are very pleased to have contributed to the study.”

Another author on the study, Professor Paul Foster at NIHR Moorfields BRC, received support from the Richard Desmond Charitable Trust via Fight for Sight.

See the complete press release.