Diabetic retinopathy is one of the most common cause of vision loss in adults suffering from diabetes and currently available medicines, though slow the progression of the diseases, do not offer complete prevention. Looking for an answer that could prevent the occurrence of diabetes-associated blindness, researchers at The Johns Hopkins University and the University of Maryland set out to look for a more effective treatment.
Diabetic retinopathy occurs when the normal blood vessels in the eye are replaced over time with abnormal, leaky, fragile blood vessels that leak fluid or bleed into the eye, damaging the light-sensitive retina and causing blindness.
One of the most used procedures to treat this disorder is laser-sealing eye blood vessels. This method effectively saves the central vision, but is many cases patients have to sacrifice their peripheral and night vision says Akrit Sodhi, M.D., Ph.D. , an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.
Pharma companies have come up with several drugs recently — bevacizumab, ranibizumab and aflibercept — that are pegged as effective treatment for diabetes-associated blindness. These drugs act on the blood vessels that cause the blindness by blocking the action of VEGF, a so-called growth factor released as part of a chain of signals in response to low oxygen levels, which stimulates the growth of new, often abnormal, blood vessels. But, subsequent studies have pegged these drugs as rather a hurdle that slows progression to proliferative diabetic retinopathy, and that they do not reliably prevent it.
Researchers of the new study published online May 25 in Proceedings of the National Academy of Sciences, started looking for an explanation as to why does blocking of VEGF doesn’t completely prevent the disease.
Postdoctoral fellow Savalan Babapoor-Farrokhran, M.D., and Kathleen Jee, a student at the school of medicine who will begin her residency in ophthalmology at the Wilmer Eye Institute at Johns Hopkins next year, tested levels of VEGF in samples of fluid from the eye taken from healthy people, people with diabetes who did not have diabetic retinopathy and people with diabetic retinopathy of varying severity.
According to the findings, while levels of VEGF tended to be higher in those with proliferative diabetic retinopathy, some of their fluid had less VEGF than did the healthy participants. But even the low-VEGF fluid from patients with proliferative diabetic retinopathy stimulated blood vessel growth in lab-grown cells.
“The results suggested to us that although VEFG clearly plays an important role in blood vessel growth, it’s not the only factor,” Sodhi says.
Carrying out a series of experiments in lab-grown human cells and mice revealed a second culprit, a protein called angiopoietin-like 4. Blocking the actions of both VEGF and angiopoietin-like 4 in fluid from the eyes of people with proliferative diabetic retinopathy, resulted in reduced blood vessel growth in lab-grown cells.
This researchers say could be the answer they were looking for. According to researchers if a drug can be found that safely blocks the second protein’s action in patients’ eyes, it might be combined with the anti-VEGF drugs to prevent many cases of proliferative diabetic retinopathy, Sodhi suggests.
The team is now investigating whether angiopoietin-like 4 might also play a role in other eye diseases, such as macular degeneration, which destroys the central portion of the retina.
