New study results show that an experimental drug may prevent or slow vision loss in people with diabetes.
The researchers at Wilmer Eye Institute, Johns Hopkins Medicine used mouse as well as human retinal organoids and eye cell lines in their investigations.
Eye conditions that cause vision loss are common complications of diabetes, affecting nearly eight million Americans — a statistic likely to almost double by 2040, according to the National Institutes of Health.
The team focused on models of two common diabetic eye conditions: proliferative diabetic retinopathy and diabetic macular oedema, both of which affect the retina.
Results of the study show that a compound called 32-134D, previously shown to slow liver tumour growth in mice, prevented diabetic retinal vascular disease by decreasing levels of a protein called hypoxia-inducible factor (HIF).
Current treatment for both proliferative diabetic retinopathy and diabetic macular oedema includes eye injections with anti-vascular endothelial growth factor (anti-VEGF) therapies. However, these treatments aren’t effective for many patients, and may cause side effects with prolonged use.
“We came to find that the drug examined in this study, 32-134D, was remarkably well tolerated in the eyes and effectively reduced HIF levels in diseased eyes,” says Akrit Sodhi, Associate Professor of Ophthalmology and the Branna and Irving Sisenwein Professor of Ophthalmology at the Johns Hopkins University School of Medicine and the Wilmer Eye Institute.
Slowed disease progression
To test 32-134D, researchers dosed multiple types of human retinal cell lines associated with the expression of proteins that promote blood vessel production and leakiness. When they measured genes regulated by HIF in cells treated with 32-134D, they found that their expression had returned to near-normal levels, which is enough to halt new blood vessel creation and maintain blood vessels’ structural integrity.
Researchers also tested 32-134D in two different adult mouse models of diabetic eye disease. In both models, injections were administered into the eye. Five days post-injection, the researchers observed diminished levels of HIF, and also saw that the drug effectively inhibited the creation of new blood vessels or blocked vessel leakage, therefore slowing progression of the animals’ eye disease.
32-134D lasted in the retina at active levels for about 12 days following a single injection without causing retinal cell death or tissue wasting.
“This paper highlights how inhibiting HIF with 32-134D is not just a potentially effective therapeutic approach, but a safe one, too,” added Sodhi. “People facing diabetic eye disease and vision loss include our family members, friends, co-workers — this is a disease that impacts a large group of people. Having safer therapies is critical for this growing population of patients.”
Further studies in animal models will be needed before moving to clinical trials.
Image shows: Artistic rendition of diabetic eye disease highlighting vascular changes (i.e., retinal neovascularisation) observed in patients with proliferative diabetic retinopathy. Credit: Isabella Sodhi, McDonogh School.
