A newly-identified protein could be key the process of retinopathy-related blindness, according to new research. The findings could lead to more effective treatments for diabetic retinopathy.
The protein, known as angiopoeietin-like 4 (ANGPTL4), is present at higher levels in the eyes of people with diabetic retinopathy. According to the researchers, blocking ANGPTL4 – and another protein, called VEGF – could be a useful way of preventing retinopathy-related blindness.
Doctors could also use a measurement of ANGPT4 levels to diagnose retinopathy at an earlier stage, which would mean the condition could be treated before it got worse.
“Ultimately, our observations provide the foundation for studies to assess inhibition of ANGPTL4 – alone or in combination with inhibition of VEGF – as a therapeutic approach for the treatment of PDR and other ocular neovascular diseases as well as for studies investigating the use of aqueous fluid ANGPTL4 as a diagnostic and/or therapeutic biomarker for these diseases,” the authors wrote.
The research will need to be developed further, then, in order for its therapeutic potential to be properly assessed. But, although preliminary, the results of this study could are promising.
Akrit Sodhi, of the Johns Hopkins University School of Medicine, explained that, although anti-VEGF treatment often slowed the onset of retinopathy, it was unable to stop it altogether.
“This suggested to us that there were other factors in the eye, in addition to VEGF, that are also pushing patients from nonproliferative to proliferative retinopathy,” Sodhi said. “Our goal was to identify these other proteins.”
The researchers gathered three groups of participants: the first had healthy eyes and no diabetes; the second contained people with diabetes but not retinopathy; the third was made of people with diabetes and retinopathy. The researchers measured VEGF levels in the eye fluid of each group.
The results were as expected: people from the third group had higher levels of VEGF in their eye fluid. More surprisingly, even those people from the third group with low VEGF levels suffered from the same eye damage associated with diabetic retinopathy, including the growth of new blood vessels. To the researchers this suggested that another protein must also be causing the disease.
After experimenting on human cells and mice, the researchers discovered ANGPTL4, potentially a significant contributor to the development of diabetic retinopathy. Regardless of their VEGF levels, people with diabetic retinopathy had consistently higher levels of ANGPTL4 than those from the other two groups.
“When we blocked this factor in fluid from patients with diabetic retinopathy, this was extremely effective for blocking the ability to promote blood vessel growth in tissue culture,” Sodhi explained.
The next step in the research is the development of drugs capable of blocking ANGPTL4.
The research was published in PNAS.

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