Research led by Associate Professor Guei-Sheung (Rick) Liu and Dr Sloan Wang from the Centre for Eye Research Australia has found that targeting an enzyme known as TAK1 could disrupt the process that can cause blindness in people with diabetes.

The findings, published in the journal Pharmacological Research, opens new avenues of research to develop therapies which could help people who don’t respond to current treatments.

“This could be an additional treatment option as it targets a pathway for the disease that current treatments don’t target,” says Associate Professor Liu.

“While the role of TAK1 has been studied as a target for cancer, this is the first time it’s been investigated for an eye disease.”

Stopping growth

Diabetic retinopathy has been estimated to affect over 100 million people worldwide.

It occurs when damage to blood vessels in the eye caused by diabetes drives the body to grow new ones to try and heal.

However, these new blood vessels are not very strong and can leak – causing more damage to the eye that will eventually lead to vision loss.

One way to manage this is anti-VEGF therapies – a treatment that blocks a growth factor protein that is increased in diabetic retinopathy.

“Although considered an effective treatment, not everyone with leaky vessels responds to these anti-VEGF therapies,” says Associate Professor Liu.

“Diabetes is a chronic condition, and the factors that contribute to these leaky blood vessels growing in the eye are very complicated.”

To try and improve this treatment Associate Professor Liu and Dr Wang investigated the role TAK1 plays in this healing process.

“We were looking for other major factors besides VEGF that we can disrupt with treatment,” says Associate Professor Liu.

Targeting TAK1

TAK1 is a kinase – an enzyme that speeds up the chemical reaction of proteins – that the body needs to send the signal to start tissue repair.

“TAK1 is an important mediator for inflammation, which contributes to some of the signals that drives blood vessel growth,” says Associate Professor Liu.

“It has already been shown to slow down cancer growth, but this is the first time it has been used in the eye.

“Through testing a medication known to inhibit TAK1 and we found it that suppressed new blood vessel formation, both in the petri dish and in a preclinical animal model.

“The work opens up a new potential avenue for therapy of diabetic eye diseases.”

Future treatments

While still many years away, future treatments for diabetic retinopathy could, alongside anti-VEGF injections, include a way to interrupt TAK1 to stop another avenue the eye can take to heal itself.

“Now that we know it works, the next step is to see how we can turn it into a treatment,” says Associate Professor Liu.

“We’d like to be able to deliver this treatment in a non-invasive way, like how we have been working to treat corneal neovascularisation through an eye drop.”

The research was funded by the National Health and Research Council of Australia, the Ophthalmic Research Institute of Australia and the National Natural Science Foundation of China.

Read the research

Wang, J.H., Lin, F.L., Chen, J. et al. TAK1 blockade as a therapy for retinal neovascularization. Pharmacol Res (2023).

https://doi.org/10.1016/j.phrs.2022.106617