Researchers in the US are developing an experimental drug to slow or halt damage to the eye from diabetic retinopathy.
The disease is one of the leading causes of vision loss worldwide. It can affect people with either type 1 or type 2 diabetes, and existing treatments are invasive and limited in scope.
Previous studies have concluded that moderating blood sugar levels through diet, exercise, and medication can help prevent or delay the progression of diabetic retinopathy, but often not before damage has been done to the eye and the vision.
Professor Lars Michael Larsen, an ophthalmologist from the University of Copenhagen, says that those studies reveal the retina is “shocked” when glucose levels fall in response to insulin therapy and glucose control.
“This has always been a paradox,” he said.
But results in studies of mice suggest that a new drug targeting hypoxia inducible factor could help.
A story in Drug Discovery News has revealed that new research from Dr Akrit Sodhi, an ophthalmologist at Johns Hopkins University School of Medicine, and his team showed that low blood sugar, or hypoglycemia, exacerbates damage to the retinal vasculature by altering gene expression in retinal cells.
In mice, an experimental drug blocked these gene expression changes and offered some protection against retinopathy, providing a potential solution to the treatment paradox.
“Diabetic retinopathy is almost expected in patients with diabetes,” said Dr Sodhi. “If it is allowed to progress, with time, it will lead to vision loss.”
In an earlier study, Dr Sodhi and his colleagues found that short intervals of hypoglycemia drove up the production of hypoxia inducible factor (HIF), a protein that regulates the expression of many different genes, including ones that control blood vessel growth.
In this new study, the researchers compared the consequences of elevated HIF in mice with and without diabetes.
The mice without diabetes tolerated HIF, but mice that were diabetic for as little as three months showed signs of vascular leakage, indicating breakdown of the blood-retinal barrier in response to hypoglycemia-induced HIF accumulation.
The experimental cancer drug 32-134D, which blocks HIF activity, prevented this effect.
“We are looking at taking this drug into patients,” said Dr Sodhi. “There’s potential benefit and also things we have to look out for with HIF inhibition.”
Prof Larsen, who was not involved in the new research, said that the results of the new study were encouraging.
“It means we should prioritise stability of glycemia,” he added, not just lowering blood sugar.
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