Researchers at the University of Michigan Kellogg Eye Centre have identified a compound that could interrupt the chain of events that cause damage to the retina in diabetic retinopathy, paving the way to a novel therapy that targets two mechanisms at the root of the disease, inflammation and the weakening of the blood barrier that protects the retina.
Diabetic retinopathy is the leading cause of blindness among working-age Americans.
In diabetic retinopathy, damage to the retina results, in part, from the activity of vascular endothelial growth factor (VEGF), a protein that weakens the protective blood-retinal barrier.
Recent drugs targeting VEGF have exhibited good response for nearly half of the patients with diabetic retinopathy. But researchers believe that there is also an inflammatory component that may contribute to the disease process.
The study, published in the Biochemical Journal identifies a specific protein common to both pathways as an important target in regulating the disease process in which blood vessels become leaky.
"In diabetic retinopathy and a host of other retinal diseases, increases in VEGF and inflammatory factors some of the same factors that contribute to the response to an infection cause blood vessels in the eye to leak which, in turn, results in a buildup of fluid in the neural tissue of the retina," says David A Antonetti, Professor, Department of Ophthalmology and Visual Sciences and Molecular and Integrative Physiology.
"This insidious form of modified inflammation can eventually lead to blindness," he said in a statement.The compound targets a typical protein kinase C (aPKC), required for VEGF to make blood vessels leak.
Moreover, Antonetti's laboratory has demonstrated that the compound is effective at blocking damage from tumor necrosis factor also elevated in diabetic retinopathy that comprises part of the inflammation.
Benefits of this compound could extend to therapies for uveitis, or changes to the brain blood vessels in the presence of brain tumors or stroke."We've identified an important target in regulating blood vessel leakage in the eye and we have a therapy that works in animal models," Antonetti said.