Scientists identify new treatment target for wet AMD

Key Takeaways

• Scientists report that a protein previously implicated in the development of atherosclerotic lesions in coronary arteries could be key to understanding why many people don’t benefit from the most used therapy for wet age-related macular degeneration (AMD). 
• The authors suggest that an antibody blocking the activity of this protein could target multiple stages of wet AMD, which might be much more efficient than current treatments.

Wet AMD is a condition characterized by abnormal blood vessel growth in the back of the eye. Anti-VEGF therapy, which blocks vascular endothelial growth factor and keeps excessive blood vessel growth at bay, is usually the first line of defense. But that treatment only works well for around a third of patients suffering from this form of AMD, says Dr. Yuqing Huo, MD, PhD, from the Medical College of Georgia. “The reason is that the excess vasculature is often accompanied by the growth of fibroblast cells,” he says. Collagen and many other proteins produced by the new fibroblast cells accumulate outside of the blood vessel cells and eventually lead to fibrosis (scarring) in the eye. This keeps the excess vasculature from being suppressed by anti-VEGF treatments. 

In a new study, Huo and his team focused on a protein called the adenosine receptor 2A (Adora2a), which has been reported to be crucial in modulating inflammation, oxygen consumption by the heart, and coronary blood flow. Adenosine, a metabolite produced by cells under conditions of stress, injuries, and lack of oxygen, can activate Adora2a to protect our body from injury. But in excess, adenosine can lead to excessive blood vessel growth.

Huo and colleagues show that high levels of adenosine-activated Adora2a can transform these excess blood vessel cells into fibroblast cells that eventually cause scarring. They further show that by either removing or blocking the activity of Adora2a in mice genetically engineered to develop fibrosis in the backs of their eyes, eye fibrosis is decreased. These novel findings were reported and recently selected as the cover image for Science Translational Medicine.

“We have previously demonstrated that blocking Adora2a can reduce excessive blood vessel growth, which happens in the early stages of AMD,” says Yongfeng Cai, PhD, a postdoctoral fellow in Huo’s lab and a member of the research team. They now have an eye toward generating an antibody that could block Adora2a. Huo added, “An antibody could really block both excessive blood vessel growth, the early stage of AMD, and fibrosis, the late stage of AMD. Our findings indicate that blocking Adora2a can certainly target multiple stages of this disease, which might be much more efficient than current treatments.”

This research was supported by the National Institutes of Health and the National Eye Institute.

Edited by Miriam Kaplan, PhD

Source: Medical College of Georgia at Augusta University, ScienceDaily, May 2, 2024; see source article