In search of genetic link in eye diseases

The Straits Times

Feb 12, 2016

By Carolyn Khew

Dr Khor Chiea Chuen was well on his way to becoming a doctor but had a eureka moment during his final year in medical school. While undergoing medical training at local institutions in 2008, he realised that about 90 per cent of the patients would get well on their own - probably even if they had not gone to hospital.

"These were the elderly or young children who had spiking fevers, coughs and colds, for instance, and doctors wanted to be careful," he explained. But it was the remaining one in 10 patients who intrigued him. This group would die without proper treatment. So he decided to turn his attention to developing the best cures for them. "If you intervene well, you can help them... I really wanted to help this 10 per cent and to know more about why they suffered certain diseases," he said.

Since the time he found his calling, Dr Khor has not looked back. After graduating from medical school, he immersed himself in research. The senior principal investigator with the Agency for Science, Technology and Research's (A*Star) Genome Institute of Singapore has been trying to find out how major eye diseases like glaucoma and macular degeneration could be hereditary - the first step towards learning how to cure these debilitating diseases.

For his work, Dr Khor has won many awards, including most recently becoming the first Singaporean to clinch the EMBO Young Investigator Programme Award in November last year. He is among only five scientists from Singapore who have won the prestigious European award since it was launched in 2000, and will receive €15,000 (S$23,500) to further his research.

Dr Khor said that, in the eyes of his colleagues, friends and collaborators, choosing to find out if there was a relationship between genetics and eye diseases like glaucoma was a "brave" thing to do. "People were thinking, why study genetic predisposition in diseases which occur in the elderly? Most of the time, such research is done on the younger population."

But he noted that ageing would be a major medical concern in the coming years. "The world's population as well as Singapore's is ageing. Strikingly, there are genetic conditions which manifest after people turn 50, and, collectively, they affect a large number of people."

It was a meeting with Professor Aung Tin from the Singapore Eye Research Institute in 2010 that led Dr Khor to suspect that glaucoma could be hereditary. Back then, Prof Aung had observed clusters of glaucoma patients in families. Dr Khor said: "It made me think: Could there be a genetic predisposition? If we could find out those who are at risk genetically, we could pick it up earlier and monitor their eyes for nerve damage."

Glaucoma, dubbed the thief of sight, affects about 3 per cent of Singaporeans aged 50 and above, and accounts for 40 per cent of blindness here. Most patients, however, do not know they have the disease until it is too late as it does not cause pain or dark spots in vision.

In 2012, Dr Khor was part of an international team comprising researchers from countries such as Britain and China which discovered three genes - PLEKHA7, COL11A1 and PCMTD1 - that were very strongly associated with increased risk of the disease. It was the first time that such a connection had been proven scientifically. Further work is needed but this initial research paves the way for identifying future drug targets.

Now, the researcher is working to better understand the mechanism behind the genetic mutations and how they cause glaucoma. These findings should be out in about two to three years, he said. Dr Khor is also doing work on exfoliation syndrome, known to cause glaucoma through a build-up of whitish material made up of protein deposits on the iris.

Studies have shown a strong association between the mutation of certain genes and the exfoliation syndrome but Dr Khor is trying to pin down the mechanism behind it.

"The key is to aim for primary prevention - don't even let the disease come up... There's this great idea that if we know about the genetics, it can help in the primary prevention, together with whatever else we know about the disease," said Dr Khor.

Work aside, he also loves nature, and takes a walk at Bukit Batok Nature Park near his home every day after work. "I like being in quiet solitude. It makes me think about things that I have not done well during the day, and I can improve on them," said Dr Khor.

Nothing excites him more than his quest for scientific knowledge. "The amazing treatments and good outcomes you see in Singapore now are because the generation of doctors before us did a lot of research to find the best standard of care. So if my generation rests on its laurels, we would still be using the old treatments years from now," said the 37-year-old, who is single. "I'm married to science - for now."