New Protein found in diabetic retinopathy may prevent the disease

Researchers have found a new protein that appears to be significantly responsible for the growth of new vessels in the eyes of patients with diabetes. Treatment targeted at this protein is likely to prevent the growth of these blood vessels and thus prevent blindness.


Currently, advanced diabetic retinopathy (also referred to as proliferative diabetic retinopathy or PDR) is treated either with laser photocoagulation to the retina that attempts to seal leaky blood vessels and slow the growth of new ones. In recent days, anti-VEGF (vascular endothelial growth factor) treatment has become the norm, since it is considered better in terms of outcome, as well as in reducing the significant complications related to laser treatment. However, anti-VEGF therapy has been noticed to only temporarily stop the disease; it also has its own risks. Also, some patients do not seem to respond at all to the therapy, which suggests other factors may likely be involved.

A group of researchers led by Dr. Akrit Sodhi of the Johns Hopkins University School of Medicine investigated other factors that might drive angiogenesis in proliferative diabetic retinopathy. Their work, which was funded by NIH’s National Eye Institute (NEI), was published in Proceedings of the National Academy of Sciences.

The researchers first compared VEGF levels in aqueous fluid from the eyes of healthy people and from patients with diabetes with and without proliferative diabetic retinopathy. While most of the patients had much more VEGF in their aqueous fluid, some had levels that were below the average for the healthy controls. The low-VEGF fluid from these patients, however, triggered as much angiogenesis in lab-grown cells as high-VEGF fluid. In fact, anti-VEGF therapy didn’t affect the ability of aqueous fluid from patients to trigger angiogenesis, despite low levels of the protein. These findings confirmed that another compound must contribute to the process.

By restricting oxygen flow to retinal cells, the team went on to discover a protein called angiopoietin-like 4 that, like VEGF, is present at much higher levels in the oxygen-deprived cells. The protein was also present at high levels in low-VEGF aqueous fluid from the eyes of patients who had recently received anti-VEGF therapy. Boosting levels of angiopoietin-like 4 greatly increased angiogenesis. In laboratory experiments, decreasing production of angiopoietin-like 4 or blocking its action reduced angiogenesis. Most importantly, inhibiting both VEGF and angiopoietin-like 4 reduced angiogenesis more than targeting just one of the proteins.

These results suggest that a drug that could block the action of angiopoietin-like 4 might help prevent proliferative diabetic retinopathy, particularly if combined with VEGF. Meanwhile, the protein might prove useful for predicting which diabetic retinopathy patients will respond to anti-VEGF therapy.

Source: National Institutes of Health & PNAS journal.

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