Reporting on their study with lab-grown human cells, researchers at The Johns Hopkins University and the University of Maryland say that blocking a second blood vessel growth protein, along with one that is already well-known, could offer a new way to treat and prevent a blinding eye disease caused by diabetes.
A summary of the study appears online May 25 in Proceedings of the National Academy of Sciences.
The disease, diabetic retinopathy , is the most common cause of vision loss in working-age adults in the United States. Diabetic eye disease 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. Forty to 45 percent of Americans with diabetes have diabetic retinopathy, according to the National Eye Institute.
Laser-sealing eye blood vessels can save central vision, but this often sacrifices peripheral and night vision, according to Akrit Sodhi, M.D., Ph.D. , an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine. Several recently developed drugs -- bevacizumab, ranibizumab and aflibercept -- can help treat these blood vessels 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 studies have shown that although these drugs slow progression to proliferative diabetic retinopathy, it does not reliably prevent it.
Looking for an explanation, 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.
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.
A series of experiments in lab-grown human cells and mice revealed a second culprit, a protein called angiopoietin-like 4. When the researchers blocked the action of both VEGF and angiopoietin-like 4 in fluid from the eyes of people with proliferative diabetic retinopathy, it markedly reduced blood vessel growth in lab-grown cells.
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.
Other authors on the paper are Brooks Puchner, Syed Junaid Hassan, Xiaoban Xin, Murilo Rodrigues, Fabiana Kashiwabuchi, Ke Hu, Monika Deshpande, Yassine Daoud, Sharon Solomon, Adam Wenick, Gerard Lutty and Gregg L. Semenza, all of The Johns Hopkins University; and Tao Ma and Silvia Montaner of the University of Maryland, Baltimore.
Shawna Williams | EurekAlert!
Do microplastics harbour additional risks by colonization with harmful bacteria?
05.04.2018 | Leibniz-Institut für Ostseeforschung Warnemünde
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy