MCG scientists identify new treatment target for leading cause of blindness

Yongfeng Cai, PhD, Yuqing Huo, MD, and Qiuhua Yang, PhD. Image credit: Michael Holahan, Augusta University

Scientists from Augusta University's Medical College of Georgia report that a gene 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 neovascular age-related macular degeneration (AMD), a leading causes of blindness.

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, because the excess vasculature is often accompanied by the growth of fibroblast cells.

In their current research, the researchers found that a high-level or persistent adenosine-activated Adora2a signal could transform endothelial cells, luminal cells of the vasculature, into activated fibroblast cells and, eventually, cause fibrosis. Fibrosis blocks the efficacy of anti-VEGF therapy.

Using genetically engineered mice that develop fibrosis in the backs of their eyes, researchers delivered an Adora2a agonist (KW6002), which binds to the receptor and blocks its function. The mice had decreased fibrosis after treatment.