A discovered protein could lead to better treatments for diabetic retinopathy


Diabetic retinopathy

Diabetic retinopathy is a diabetes complication that affects the eyes. The disease damaged to the blood vessels of the light-sensitive tissue in the retina. Diabetic retinopathy may cause no symptoms or only mild vision problems. Eventually, it can cause blindness, and also have implications for other diseases, including cancer.

Researchers at University of Utah Health identified an ADP-ribosylation factor 6 (ARF6) protein that inhibited reduces diabetic retinopathy.

Study first co-author, Weiquan (Wendy) Zhu, Ph.D., explained, we identified a compound NAV-2729 that inhibits ARF6, which is crucial for the development of diabetic retinopathy.

For studies, researchers injecting NAV-2729 into the eyes of rodents that treat diabetic retinopathy. The researchers identify a signaling cycle that promotes two features of diabetic retinopathy, increased blood vessel leakage and the birth of new blood vessels.

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ARF6 Protein

The study has uncovered the role that ARF6 plays in the control of vascular endothelial growth factor (VEGF), a signaling protein that plays a key role in the development of diabetic retinopathy.

However, a treatment for diseases in which patients receive a monthly injection of anti-VEGF drugs directly into the eye. But the treatment reduces inflammation, only works for around 40 percent of patients. ARF6 protein increase and maintain a receptor for VEGF, which stimulates a series of cascading responses in the eye. ARF6 arranges multiple inflammatory signals that contribute to inflammation common in many diseases, including diabetic eye disease.

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According to these results, researchers 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.

The researchers also identified ARNO and GEP100 proteins that help to maintain the signals by activating ARF6 at two different cell locations.

When ARNO activates ARF6, it ferries the VEGF receptor into the cell, allowing its signal to be amplified. When GEP100 activates the protein, it causes it to ferry it back to outside the cell, effectively “recycling” it for reuse in a new signaling cycle.

However, further studies needs to be done to determine the long-term effects of the treatment and establish whether it is safe and effective in humans.

More information: [The Journal of Clinical Investigation]