A $600,000 grant from the Australian Government’s Medical Research Future Fund (MRFF) will help to refine a new gene treatment that could restore lost vision.

The funding from the MRFF’s Stem Cells Therapies Mission will support CERA’s Cellular Reprogramming Research, led by Associate Professor Raymond Wong.

Associate Professor Wong is working on a way to regenerate dead retinal cells using the retina’s own stem cells – the Müller glia cells.

Millions of tiny light-sensing cells known as photoreceptors line the retina at the back of the eye and send visual signals to the brain, enabling us to see.

When they are damaged or die, vision loss occurs.

The loss of photoreceptor cells is common in many retinal diseases, including retinitis pigmentosa and age-related macular degeneration (AMD).

An estimated 190 million people worldwide have retinal degenerative diseases with photoreceptor losses.

So far there is no effective treatment or cure to treat the blindness caused by these diseases.

However, Associate Professor Wong is working on a gene therapy solution.

Although some animals such as fish and birds have a natural ability to regenerate cells in the retina if they are damaged, this ability has been either lost or suppressed in humans, says Associate Professor Wong.

“Our aim is to develop a gene therapy to stimulate retinal regeneration in people.

“The MRFF’s funding provides critical support to optimise what we have learned in the lab, which we need to do before we can translate it into a therapy that can be tested in a clinical trial with patients.”

Reprogramming cells

Associate Professor Wong says this new project will build on five years of promising preclinical research into reprogramming cells using genes to control how the cells behave.

“The new funding will help us to improve the technology we use to reprogram stem cells – the Müller glia cells in the retina – to become photoreceptors.

“We are using human Müller glia cells in lab dishes to optimise the best genes for reprogramming. Then we test the best genes in preclinical studies using animal models,” explains Associate Professor Wong.

“Our goal is to be as specific as we can when we deliver the gene therapy to target the retina. We are doing more experiments to optimise this, to make sure it is as safe and efficient as possible.”

Investigating AMD

Associate Professor Wong is also leading collaborative research with the University of Melbourne, the Lions Eye Institute and other national collaborators to identify the role of different genes associated with AMD.

In 2023 Associate Professor Wong and his team published two papers that focused on two genes, TMEM97 and POLDIP2, and their role in AMD.

To identify the genes’ function, the team created a lab model of human retinal pigment epithelium cells (RPE) – the cells affected in AMD.

Then they used gene editing technology to ‘switch off’ the two genes and discovered they had a key role in maintaining cell health.

Both genes help manage oxidative stress in cells, which increases as we get older, and can damage cells in the retina, leading to vision loss.

“For the first time, we understand the function of these genes that are associated with AMD in human retinal cells. This means we have identified potential gene targets for drug treatments to delay or halt the disease,” says Associate Professor Wong.

This story was originally published in People in focus: Annual Review 2023.