Research Highlights

The glaucoma-causing gene that also protects against it

Published online 29 May 2017

A rare form of a gene implicated in glaucoma has a surprisingly strong protective effect against it.

Nadia El-Awady

Scientists have sequenced the genes LOXL1 and CACNA1A implicated in an age-related condition called exfoliation syndrome (XFS).

The gene LOXL1 was the first to be identified as being associated with XFS, in which abnormal extracellular material is produced and accumulates in tissues in excessive amounts. This can lead to glaucoma and is a major cause of blindness globally.

The international team of researchers examined 5,570 people with the condition and 6,279 people without it from nine countries. They found that a rare form of LOXL1 provided 25 times more resistance to XFS-glaucoma compared to people without the gene variant1.

This very strong protective effect was not absolute: two of the XFS cases studied had this variant of the gene, but they also carried a gene copy that makes them more susceptible to the disease. 

“Our data suggests that [the LOXL1 variant] stabilizes the extracellular matrix by increasing elastin and fibrillin deposition,” explains Chiea Chuen Khor from the Genome Institute of Singapore. “This in turn improves cell-to-cell adhesion, which could be a good thing in aging cells, and prevents cells from exfoliating off the extracellular matrix basement membrane.”

The team also analysed the genomes of 9,035 XFS cases and 17,008 people without the condition in 24 countries across six continents, identifying five new genes associated with the disease. All five genes are known to be involved in the aging process. 

“Our next step is to try to study LOXL1 in more detail in human cells and to try to make an animal model for it. Our long-term goal is to see if we can develop a therapy against XFS based on our knowledge of the strongly protective rare … mutation at LOXL1,” says Khor.


  1. Aung, T. et al. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat. Genet. (2017).