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Protein discovery could reduce vision loss in diabetic retinopathy

A key protein involved in diabetes-related vision loss could hold promise for treating diabetic retinopathy, researchers say.
University of Utah scientists believe the ADP-ribosylation factor 6 (ARF6) protein could be targeted to reduce the severity of diabetic retinopathy. They also believe it could also have implications for treating diseases such as cancer.
In studies on mouse models of diabetes the researchers uncovered the role of ARF6 in the control of vascular endothelial growth factor (VEGF), a signalling protein that plays a primary role in the development of diabetic retinopathy.
Diabetic retinopathy develops as a result of uncontrolled blood sugar levels over a long period of time, a treatment of which is monthly injections of anti-VEGF drugs into the eye.

According to senior author senior author Dr. Dean Li, “ARF6 acts like a traffic cop at a busy intersection within a cell. ARF6 orchestrates multiple inflammatory signals that contribute to inflammation common in many diseases, including diabetic eye disease.”
The team also uncovered two separate proteins, ARNO and GEP100, which help ARF6 to activate VEGF, causing greater levels of inflammation.
Subsequently, the researchers went about blocking these proteins, and identified a compound called NAV-2729 that inhibits ARF6. When they injected this into the eyes of rodents that had been modified to develop diabetic retinopathy, key features of the disease began to disappear.
“We think these results are important because they identified a mechanism by which ARF6 controls VEGF receptor signalling and therefore may have much broader implications, extending to other diseases that involve VEGF receptor activatio, such as cancer,” said the researchers.
Blocking this protein could not only help to reduce diabetic retinopathy and sight loss, but also extend to diseases such as cancer which also involve VEGF receptor activation.
However, these findings cannot be validated until the process is tested successfully and safely on humans, and further work will need to be done on this front.
The study was published in the Journal of Clinical Investigation.

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