Genetic detectives: finding the causes of eye disease

CERA’s clinical genetics team is zeroing in on the causes of inherited eye diseases, then devising new treatments and screening tools to preserve vision and prevent blindness.


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Inherited eye diseases are common and complex. Inherited retinal diseases, for example, are the leading cause of blindness in people of working age, with glaucoma the most common in older people. As with age-related macular degeneration (AMD), we know that the number of people affected by glaucoma will grow as our population ages.

Understanding the genetic basis for these blinding diseases is key to finding a cure or a way to prevent vision loss, says Professor Alex Hewitt, Head of Clinical Genetics at CERA.

Inherited eye diseases can be caused by a fault or ‘mistake’ in a single gene, or in several genes.

“The faulty gene is a sole event, a bit like a single car accident,” says Professor Hewitt, “and there are common complex genetic diseases that are more like a general traffic jam and congestion around the city.”

CERA’s clinical genetics team investigates the genes responsible for common inherited eye diseases like glaucoma and retinitis pigmentosa and rare diseases such as Leber’s Hereditary Optic Neuropathy (LHON). Where the genes or gene variants are identified, the next goal is to edit, delete or repair these faults or explore another way to stop a disease progressing.

The team also translates its findings into screening tools and gene therapies that can be tested and proven in the clinic.

Rapid developments


Revolutionary discoveries in genetic engineering have now made it possible to modify DNA, says Research Fellow Dr Sandy Hung.

It may sound space age, but the invention of the CRISPR gene editing system in 2012 was in fact inspired by a natural process found in bacteria. The CRISPR gene editing system finds, attacks and destroys an enemy virus by cutting away the DNA of the virus.

“Scientists modified this molecular machinery to target any sequence of DNA, including sequences containing disease-causing mutations in human cells,” says Dr Hung.

CRISPR enables researchers to target specific genetic mutations, and delete or correct them.

Dr Hung and the team in Professor Hewitt’s laboratory are currently using a CRISPR base editing system to target and change the point mutation in the DNA sequence, as part of their research into LHON.

“When you cut the entire DNA strand you might not get the modification or cellular repair you want,” says Dr Hung. Refining and developing these tools is a major part of the team’s work.

“Better tools are coming out all the time.”

From the lab to the clinic


Earlier this year, CERA was part of a research collaboration which discovered 107 genes that increase a person’s risk of developing glaucoma. “For the first time we’ve been able to clearly show that particular genetic ‘loads’ have different likelihoods of developing glaucoma,” says Professor Hewitt.

CERA worked with the QIMR Berghofer Medical Research Institute and Flinders University, as well as ophthalmologists and patients around the country. And there are more genes to be identified.

By comparing the genomes of people with and without the disease, through a process called Genome Wide Association Scanning, the team is searching for more genes that contribute to disease risk.

They are also investigating the cells that regulate pressure in the eye, which is a major risk factor for developing glaucoma.

The team has now begun developing a test to identify an individual’s glaucoma risk, and hopes to have it ready for clinical use within the next two years.

Down the track, it could be used for population-wide screening.

“This research is very exciting,” says Professor Hewitt. “It’s hard to predict what the next breakthrough will be, but we’re certainly motivated to understand why some people get disease, and what we can do about it.”

Professor Hewitt’s research is supported by the National Health and Medical Research Council and the Ophthalmic Research Institute of Australia. Dr Hung’s research is supported by the Mito Foundation.

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