Researchers at the Medical College of Georgia (MCG) have found that targeting a specific receptor in the eye may benefit many patients with neovascular age-related macular degeneration, who don’t respond well to current treatments.
Age-related macular degeneration is a leading cause of blindness worldwide and occurs mostly in the elderly and people with metabolic diseases, such as diabetes and obesity. It is characterized by increased blood vessel growth in the eye, damaging the macula at the back of the eye, which is essential for translating light into image signals.
Current treatments target this excessive blood vessel growth, however, only a third of patients with age-related macular degeneration benefit from these.
“The reason is that the excess vasculature is often accompanied by the growth of fibroblast cells,” explained Yuqing Huo, Director of the Vascular Inflammation Program at MCG’s Vascular Biology Center.
These fibroblast cells produce collagen and other proteins that collect around the blood vessel cells and cause scarring in the eye, also known as fibrosis. In their study, published in the journal Science Translational Medicine, the researchers focused on the adenosine receptor 2-A (Adora2a), found in blood vessels, immune cells, and the brain.
The researchers discovered that a continuous or high-level signal of adenosine-activated Adora2a could turn endothelial cells—which are part of the vasculature—into active fibroblast cells, leading to fibrosis. They hypothesized that blocking Adora2a may reverse or prevent fibrosis in the back of the eye.
In mice with laser-induced retinal injury or genetically induced age-related macular degeneration, the researchers deleted the gene encoding Adora2a. They found that the lack of Adora2a prevented fibrosis in the eyes of both mouse models. Moreover, the researchers blocked the function of Adora2a using an antagonist of the receptor and demonstrated decreased fibrosis in the eye.
“We have previously demonstrated that blocking Adora2a can reduce excessive blood vessel growth, which happens in the early stages of age-related macula degeneration,” said Yongfeng Cai, a postdoctoral fellow in Huo’s lab and a member of the research team.
As a next step, the MCG researchers want to develop an antibody that can block Adora2a and prevent fibrosis in age-related macula degeneration.
“The antibody could be delivered via an injection to the back of the eyes, an approach often used in eye clinics, to block the activation of adenosine to Adora2A,” Huo explained.
“An antibody could really block both excessive blood vessel growth, the early stage of age-related macula degeneration, and fibrosis, the late stage of age-related macula degeneration. Our findings indicate that blocking Adora2a can certainly target multiple stages of this disease, which might be much more efficient than current treatments.”
