Scientists from the Medical College of Georgia have made a groundbreaking discovery that could revolutionize the treatment of neovascular age-related macular degeneration (AMD). AMD is a prevalent eye condition, particularly among seniors and those with metabolic diseases, which leads to abnormal blood vessel growth at the back of the eye, resulting in damage to the macula.
The standard treatment for AMD is Anti-VEGF therapy, aiming to curtail unnecessary blood vessel growth. However, this therapy only proves effective for approximately one-third of AMD patients. The ineffectiveness of the treatment is attributed to the growth of fibroblast cells that accompany excessive vasculature, leading to fibrosis or scarring in the eye which can’t be suppressed by anti-VEGF treatments.
Dr. Yuqing Huo, the Director of the Vascular Inflammation Program at MCG’s Vascular Biology Center, and his team have identified the adenosine receptor 2A (Adora2a) as a potential target for preventing the transformation of endothelial cells into activated fibroblast cells, which lead to fibrosis. Adora2a is an adenosine receptor found in high levels in the brain, immune cells, and blood vessels, playing a crucial role in modulating inflammation, myocardial oxygen consumption, and coronary blood flow.
The team’s research revealed that high or persistent adenosine-activated Adora2a signals could cause endothelial cells to transform into activated fibroblast cells, leading to fibrosis. By blocking Adora2a, this transformation could potentially be prevented.
The team put their theory to the test by using genetically engineered mice that develop fibrosis in their eyes. They administered an Adora2a agonist (KW6002) to these mice, which binds to the receptor and inhibits its function. The results were promising, with the mice showing a decrease in eye fibrosis. The team’s findings were recently featured on the cover of Science Translational Medicine.
The researchers are now working on creating an antibody that could recognize Adora2a. The idea is to deliver this antibody through an injection to the back of the eye, a common procedure in eye clinics. The antibody could potentially block both excessive blood vessel growth and fibrosis, targeting multiple stages of AMD, which could be far more effective than current treatments.
This pioneering research has been supported by a National Institutes of Health K99 award to Dr. Qiuhua Yang and funds from the National Eye Institute.
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