Norrin treatment prevents vision loss in diabetic rats, study finds

University of Michigan researchers found that treating diabetic rats with the molecule norrin prevents vision loss, reduces neural cell loss, and halts retinal inflammation. Current anti-VEGF therapies require frequent injections and fail in half of patients. The findings have led EyeBio and Merck to develop clinical trials targeting norrin receptors, potentially yielding the first new diabetic retinopathy treatment class in 16 years.

Norrin treatment results in diabetic rats

• ▪In diabetic rats, norrin treatment prevented retinal cell death and inflammation in both early and late stages of diabetes, and starting treatment after initial vision loss halted further decline.
• ▪A University of Michigan study published in Diabetes found that injecting diabetic rats with the molecule norrin prevented vision loss and reduced neural cell loss.

Norrin's role in blood-retinal barrier restoration

• ▪University of Michigan researchers found that rats exhibit decreased natural norrin levels alongside reduced vision after developing diabetes, while prior cell studies showed norrin reverses VEGF barrier breakdown.
• ▪University of Michigan researchers identified several genes affected by norrin treatment and are studying how these genes contribute to blood-retinal barrier restoration.

Drug development efforts with EyeBio and Merck

• ▪Research from David Antonetti's lab helped EyeBio and Merck initiate clinical trials for drugs that increase activity in cell receptors responding to norrin.
• ▪David Antonetti assisted Merck in developing a potential drug for treating adults with macular edema, a primary driver of vision loss in diabetic retinopathy patients.

Diabetic retinopathy and anti-VEGF limitations

• ▪Diabetic retinopathy is an eye disease caused by damage to retinal blood vessels that can lead to blindness if underlying diabetes remains unmanaged.
• ▪Current anti-VEGF therapies for diabetic retinopathy require multiple injections and fail to fully manage the condition in half of treated patients.
• ▪In diabetic retinopathy patients, excess vascular endothelial growth factor (VEGF) causes abnormal, leaky blood vessel growth and increases vascular permeability, driving vision loss.