In brief

A gene associated with Alzheimer's disease has been linked to open-angle glaucoma, suggesting a common pathway between the two conditions.

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Seeing glaucoma in a new light

14 Sep 2020

A large-scale genome study suggests that Alzheimer’s and an eye disorder called glaucoma share a common disease development pathway.

When pondering over the question of which of our five senses is most important, classical philosophers like Plato and Aristotle chose the sense of sight, because of its importance in our appreciation and understanding of the world.

Unfortunately, vision loss is a common problem facing the elderly due to a disease called glaucoma. Its root cause is traditionally understood to be increased pressure in the eyeball, which leads to optic nerve damage. While glaucoma can impact people of any ancestry, a form of glaucoma called open-angle glaucoma manifests more severely in individuals of African ancestry, although the reason for this is poorly understood.

To gain insight into the cause of this disparity, Chiea Chuen Khor, a Senior Principal Investigator at A*STAR’s Genome Institute of Singapore (GIS), along with collaborators in the Genetics of Glaucoma in People of African Descent Consortium, performed a genome-wide association study to identify genetic variants specific to individuals of African ancestry that could be linked to increased risk of open-angle glaucoma.

The group first used genome-wide genotyping to scan the entire human genome for more than one million single nucleotide polymorphisms (SNPs), which are single-letter variations in DNA. In particular, the team found that a SNP in a gene named APBB2 was strongly associated with an increased risk of primary open-angle glaucoma. With more than 26,000 participants, the study’s size enabled them to identify APBB2 with strong statistical certainty, explained Khor, who is the last author of the study published in JAMA.

Intriguingly, APBB2 is known to be linked to the production of a type of protein called beta-amyloid, which has been implicated in Alzheimer’s disease. Armed with this clue, researchers next examined retinal and visual cortex tissue. They found that individuals who carried two copies of the APBB2 genetic variant had more beta-amyloid in these tissues, suggesting a common pathway in disease development between open-angle glaucoma and Alzheimer’s.

“Our findings suggest that glaucomatous optic nerve damage can be due to amyloid pathology, and not just due to pressure,” Khor highlighted.

Future studies will involve much larger sample sizes to confirm a causal association between amyloid buildup and glaucoma, said Khor, who hopes that the work will lead to new therapeutic strategies for glaucoma. He also noted that pharmaceutical companies such as Galimedix have already developed eye drops to reduce amyloid buildup that are now in clinical trials. Taken together, these developments strongly suggest that drugs targeting amyloid deposition could help retard glaucomatous nerve damage, he said.

The A*STAR-affiliated researcher contributing to this research is from the Genome Institute of Singapore (GIS).

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Genetics of Glaucoma in People of African Descent (GGLAD) Consortium. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry. JAMA 322, 1682-1691 (2019). | article

About the Researcher

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Chiea Chuen Khor

Senior Principal Investigator

Genome Institute of Singapore
Chiea Chuen Khor obtained his PhD from the University of Oxford in 2006 and his MBBS from the National University of Singapore in 2009. He is currently a Senior Principal Investigator and Group Leader for the Division of Human Genetics at the Genome Institute of Singapore. His research interests are centered on understanding predisposing factors for disease in otherwise healthy people, with the aim of discovering new ways to help patients.

This article was made for A*STAR Research by Wildtype Media Group