Monash researchers show drug may prevent diabetes-induced vision loss

Dr Devi Deliyanti and Professor Jenny
Wilkinson-Berka are first and last authors
on the paper investigating a drug which
reduces oxidative stress in the retina.

by Anne Crawford

Scientists in Monash University’s Department of Diabetes have demonstrated that a novel drug that suppresses oxidative stress protects the retina against diabetes-induced damage and may prevent vision loss.

Globally, an estimated 70 million people have retinopathy caused by diabetes. The disease is the leading cause of blindness in young adults.

People with diabetes have high levels of glucose in their blood which stimulates oxidative stress, a process that causes damage to many cell types and ultimately cell death.

Central Clinical School scientists led by Professor Jennifer Wilkinson-Berka tested the drug dh404 in animal models and found it helps prevent this damage. The drug activates a powerful protein called nrf2 (nuclear factor erythroid-2-related factor 2), a master regulator of antioxidant activity in the body.

“Nrf2 is an important defence mechanism against oxidative stress,” Professor Wilkinson-Berka said. “We know that if we can boost it we can reduce the ‘bad guys’ – the free radicals that cause it.”

Oxidative stress is implicated in many other diseases including Alzheimer’s Disease, cancers, atherosclerosis, heart and kidney disease.

There are a number of ways to reduce it, among them consuming foods including blueberries, green tea and red wine, which have anti-oxidant properties. However, a drug was needed in the case of disease such as diabetes, Professor Wilkinson-Berka said.

The paper was published in the online journal ‘Investigative Ophthalmology & Visual Science’ last month.

The researchers, who have a reputation for ground-breaking work in oxidative stress and eye disease, were asked to test dh404 by a US pharmaceutical company. “We have all the tools, the resources and the animal models for this research,” Professor Wilkinson-Berka said. “People notice your work – the companies come to you.

“You never know when you put a drug into a disease model – diabetes is complicated – but this one was extremely successful,” Professor Wilkinson-Berka said. “I think it’s a very promising approach for treating diabetic retinopathy.”

First author Dr Devy Deliyanti, who developed the animal models for the study, said dh404 was potent. “You only need a small amount.”

The drug is expected to be adapted by the company for clinical use.

Professor Wilkinson-Berka and Dr Deliyanti have conducted research together for about seven years, producing a number of papers in this area together with colleagues.

In a paper published last year the researchers revealed the previously unknown existence of a disease-fighting immune cell in the eye that pointed to potential novel ways of treating severe eye disorders in premature babies and diabetic adults. Clinical studies in patients with diabetic retinopathy based on that research are underway.

Reference
Deliyanti D, Alrashdi SF, Tan SM, Meyer C, Ward KW, de Haan JB, Wilkinson-Berka JL. Nrf2 Activation Is a Potential Therapeutic Approach to Attenuate Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):815-825. doi: 10.1167/iovs.17-22920.