Targeting cellular pathways controlled by norrin can be used as a therapeutic strategy to prevent vision loss in patients with diabetes
In a new study published in the journal Diabetes, University of Michigan researchers showed that treatment with the molecule norrin can prevent vision loss from diabetic retinopathy in diabetic rat models.
Current therapies for diabetic retinopathy target vascular endothelial growth factor, or VEGF, a protein that causes new blood vessels to form. VEGF also increases blood vessel permeability or the capacity to allow water and nutrients to move in and out of the bloodstream into tissues.
In patients with diabetic retinopathy, excess VEGF causes the growth of abnormal, leaky blood vessels, both leading to vision loss. Although anti-VEGF agents are commonly used to treat diabetic retinopathy, it requires several injections and fails to fully manage half the treated patients.
“There is an urgent need for new therapies that can help preserve vision in patients with diabetic retinopathy,” said David Antonetti, PhD, Research Professor of Ophthalmology and Visual Sciences at Kellogg Eye Center.
“We have been working on the effects of norrin for several years and these results will help develop new therapies that can prevent vision loss.”
Preventing vision loss
In previous studies, the team showed that norrin can reverse the effects of VEGF on the blood vessel barrier in cells. In the current study, they found that after rats developed diabetes, their levels of norrin decreased and this was accompanied by decreased vision. When they injected these rats with norrin, the researchers could prevent vision loss.
“We are excited that norrin treatment can also reduce the loss of nerve cells involved in vision in diabetic rats,” said Laura González-González, Postdoctoral Fellow in the Antonetti lab.
Treatment with norrin also prevented retinal cell death and inflammation, both in early and late stages of diabetes. Starting norrin treatment even after vision loss prevented further loss in the diabetic rats. These results suggest that norrin can potentially help prevent vision loss in patients with diabetes.
The team identified several genes that were affected by norrin treatment, and they are working on understanding how they contribute to barrier restoration.
Clinical trials and retinal blood vessels
The work done by the Antonetti lab has helped target identification for a new diabetic retinopathy treatment method.
To this end, their work helped EyeBio and Merck develop clinical trials for drugs that can increase the activity of cell receptors that respond to norrin.
Antonetti was also involved in helping Merck develop a drug for treating adults with macular oedema, a major driver of vision loss in patients with diabetic retinopathy.
If successful, this will be the first new therapy for the condition in 16 years.
Original written by Ananya Sen
Source: University of Michigan
