Diabetic Retinopathy Driven by VEGF-Related Protein

More than one-third of Americans with diabetes will develop diabetic retinopathy, which is characterized by permanent vision loss due to leaky blood vessels in the eye. Since there is no cure and treatment options are limited, preventing the condition is crucial.

Researchers have recently discovered that the ARF6 protein may be involved with diabetic retinopathy and inhibiting the protein was observed to reduce the condition, according to a new study published by The Journal of Clinical Investigation.

“What is exciting about this study is that we and our collaborators identified a compound (NAV-2729) that inhibits ARF6, which is crucial for the development of diabetic retinopathy,” said co-first author Weiquan Zhu, PhD.

Included in the study were rodent models of diabetic retinopathy administered ocular injections of NAV-2729.

When injected with the drug, blood vessel leakage and overgrowth were significantly reduced, according to the study. These factors are hallmarks of diabetic retinopathy.

However, more research is needed to determine the long-term effects of the therapy and how humans would respond.

“ARF6 acts like a traffic cop at a busy intersection within a cell,” said senior author Dean Li, MD, PhD, vice president, head of translational medicine at Merck. “ARF6 orchestrates multiple inflammatory signals that contribute to inflammation common in many diseases, including diabetic eye disease.”

The authors report that ARF6 amplifies and maintains the vascular endothelial growth factor (VEGF) receptor, which plays a role in diabetic retinopathy.

Patients with the condition typically receive monthly anti-VEGF injections in the eye to lower inflammation, but the therapy has had limited success. Compared with the success rate of 40% for current therapies, NAV-2729 injections may more effectively reduce blood vessel leakage, according to the study.

“Diabetic retinopathy can develop over time, leading to dramatic vision loss that may not be improved with glasses,” said study contributor M. Elizabeth Hartnett, MD. “New treatments are needed because diabetic retinopathy is increasing worldwide and anticipated to increase more in the next decades.”

The authors also discovered that the proteins ¾ GEP100 and ARNO ¾ are crucial to the signaling process since they activate ARF6 to continue the cycle, according to the study.

“We think these results are important because they identified a mechanism by which ARF6 controls VEGF receptor signaling and therefore may have much broader implications, extending to other diseases that involve VEGF receptor activation, such as cancer,” said corresponding author Shannon Odelberg, PhD.