Fight for Sight: Scientists identify 3 novel genetic risk factors for primary open angle glaucoma

14 January 2016
Source: Fight for Sight

An international team of researchers has discovered 3 new inherited risk factors for the most common form of glaucoma. Variations in the genes TXNRD2, ATXN2 and FOXC1 are associated with primary open angle glaucoma (POAG) and present novel targets for screening, prevention and treatment. The study was published in Nature Genetics with part-funding from Fight for Sight.

Glaucoma is a leading cause of irreversible blindness worldwide. The most common form – primary open-angle glaucoma, or POAG – involves gradual sight loss due to damage and eventual death of the retinal ganglion cells that make up the optic nerve. This damage is usually caused by high intraocular pressure as micro channels in the eye’s drainage system become blocked over time.

The current research was a meta-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 cases and 42,000 controls were included, primarily from people with white European ancestry.

Results link the gene FOXC1 to common adult-onset glaucoma for the first time. Genetic sequence mutations in this region are already known to cause anterior segment dysgenesis, in which the front of the eye does not develop normally, and an early onset glaucoma. FOXC1 also has a role in regulating the response to oxidative stress.

Neither ATXN2 nor TXNRD2 has previously been linked to any glaucoma-type trait. However ATXN2 may be involved in neuro-degeneration. Certain faults in this gene are known to cause spinocerebellar ataxia type 2 with optic atrophy and can contribute to developing amyotrophic lateral sclerosis. TXNRD2 produces a protein necessary for proper function of the mitochondria – the power-house battery compartments inside cells. It is the first mitochondrial protein to be linked to glaucoma.

Dr Pirro Hysi is a genetic epidemiologist at King’s College London who participated in the study, supported by 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.”

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.”

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 from the NIHR Moorfields BRC, received support from the Richard Desmond Charitable Trust via Fight for Sight.

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