New glaucoma genes discovered

A large international team of scientists, including Australians, have brought together the data from 14 genetic studies of the most common form of glaucoma - the leading cause of blindness worldwide - and identified three areas of genetic code that are associated with an increased risk of developing the disease. The findings, which were published in Nature Genetics, should help us understand what causes glaucoma, and in the development of new treatments, they say.

Glaucoma is a group of conditions that damage the optic nerve, the bundle of nerve fibers connecting the eye to the brain.

In primary open angle glaucoma, the most common type, pressure inside the eye is increased in most of the cases. If detected early, glaucoma associated vision loss can often be prevented with surgery or eye drops to lower pressure.

The underlying causes of primary open angle glaucoma remain poorly understood, but likely involve the interaction of many genes with environmental influences.

The researchers compared the DNA of 3,853 people of European ancestry with primary open-angle glaucoma to a similar group of 33,480 people without it.

The analysis showed that specific variations in the genes FOXC1, TXNRD2, and ATXN2 are associated with glaucoma. Additional analyses of datasets from Europe, Australia/New Zealand, and Singapore also found associations between glaucoma and these gene variants. All three genes are expressed in the eye, and TXNRD2 and ATXN2 are active in the optic nerve.

Scientists had already identified an association between FOXC1 and glaucoma, but only in rare cases of severe early-onset glaucoma.

For TXNRD2 the authors found that it is an enzyme that protects energy producing components in our cells, the mitochondria, against toxic byproducts from normal metabolism.

The study suggests that people with TXNRD2 gene variants may have a reduced ability to protect mitochondria from this oxidative stress, leading to optic nerve cell death.

Little is known about the normal function of ATXN2. Mutations of the gene are implicated in a rare disorder called spinocerebellar ataxia 2 that causes loss of balance and coordination.

Interestingly, ATXN2 is the third gene associated with both glaucoma and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. However, there is no evidence that people with glaucoma are at greater risk of developing ALS.