Medical College of Georgia scientists have discovered a gene that is linked to the development of atherosclerotic lesions in coronary arteries, which could help explain why many individuals do not benefit from the most commonly used therapy for neovascular age-related macular degeneration (AMD), a leading cause of blindness. AMD is characterized by abnormal blood vessel growth in the back of the eye, leading to damage to the macula, which is responsible for translating light into image signals. Anti-VEGF therapy is the primary treatment for AMD, but it only works well for about a third of patients due to the growth of fibroblast cells that accumulate collagen and lead to fibrosis in the eye, preventing the suppression of excess blood vessel growth.
Dr. Yuqing Huo and his team at MCG’s Vascular Biology Center believe that targeting the adenosine receptor 2A (Adora2a) could be the key to preventing the growth of fibroblast cells and subsequent fibrosis in AMD patients. Adora2a is found in high levels in the brain, immune cells, and blood vessels, and is crucial in modulating inflammation and other processes. Adenosine, a metabolite produced by cells under stress, can activate Adora2a to protect the body from injury, but excessive adenosine can lead to excessive blood vessel growth. By blocking this receptor, the researchers hope to prevent the transformation of endothelial cells into fibroblast cells and reduce fibrosis in the eye.
Using genetically engineered mice that develop fibrosis in their eyes, the researchers found that delivering an Adora2a agonist, which binds to the receptor and blocks its function, led to decreased fibrosis in the eyes of the mice. Mice with Adora2a removed from only the vascular endothelial cells also demonstrated decreased fibrosis. The team is now considering developing an antibody that could recognize Adora2a and be delivered via injection to block the activation of adenosine to Adora2a in the eyes. This approach could target both excessive blood vessel growth in the early stage of AMD and fibrosis in the late stage, making it more efficient than current treatments.
Previous research by the team has shown that blocking Adora2a can reduce excessive blood vessel growth in the early stages of AMD. With their current findings, they hope to develop an antibody that can target multiple stages of the disease, offering a more comprehensive treatment approach. This research has been supported by a National Institutes of Health K99 award to Dr. Qiuhua Yang and funding from the National Eye Institute. The team’s discovery of the role of Adora2a in AMD pathophysiology could lead to new and more effective treatments for this blinding condition.
