Researchers from Johns Hopkins Medicine have homed in on a new pathway for treating diabetic macular edema. These findings were published in September in The Journal of Clinical Investigation.
Macular edema is a form of swelling and inflammation in people with diabetes when blood vessels in the eye leak fluids into the portion of the retina that controls detailed vision. Current therapies for this disease block the protein VEGF, which contributes to abnormal blood vessel growth. However, because the treatment is not adequate for more than half of patients with diabetic macular edema, investigators have long suspected that more factors drive vision loss in these patients.
The study finds evidence for another signaling protein at play, known as angiopoietin-like 4. Investigators have found that angiopoietin-like 4 acts both independent of, and synergistically with, VEGF activity, and they identified a potential way to block it.
When human blood vessel tissue cells were exposed to low levels of VEGF and angiopoietin-like 4 in combination, the researchers observed a synergistic effect on vascular cell permeability, and a doubled amount of leakage from retinal vessels in mice. They then found that angiopoietin-like 4 did not bind to the classic VEGF receptor, but another less studied one called neuropilin.
Injecting a soluble fragment of the neuropilin receptor into the eyes of a diabetic mouse model resulted in a twofold increase in retinal vascular leakage. The treated diabetic mice showed approximately half of the blood vessel leakage as mice who did not receive the treatment, similar to the nondiabetic mice.
This phenomenon was further tested in primary blood vessel cells collected from the eyes of patients with diabetic macular edema. One group of such cells was exposed to the soluble receptor neuropilin. The researchers say they observed a marked decrease in the diabetic macular edema cells treated with the receptor compared to untreated cells.
“This gives us some confidence that this approach will work in human eyes as well,” said Akrit Sodhi, M.D., Ph.D., who led the study. He cautioned, however, that clinical use of a treatment based on their findings will require many more years of research. His team hopes to follow up by taking a look at the molecular interactions between angiopoietin-like 4 and the neuropilin receptor. Doing so may lead to a refined match that can bind up as much vision-threatening angiopoietin-like 4 in the eye as possible.
Full news release: https://www.hopkinsmedicine.org/news/newsroom/news-releases/helper-protein-worsens-diabetic-eye-disease
Source: John Hopkins Medicine