Scientists find potential treatment target for leading cause of blindness
US scientists have found answers to why treatment for neovascular age-related macular degeneration (AMD) — a leading cause of blindness — does not benefit all; and also developed a potential antibody treatment.
AMD is a condition characterised by abnormal blood vessel growth in the back of the eye.
Older age, diabetes, obesity, and many other chronic metabolic diseases lead to excessive vascular growth and damage to the macula — the part of the eye that translates light into image signals.
The first line of defence is usually the Anti-VEGF therapy, which blocks vascular endothelial growth factor and keeps excessive blood vessel growth at bay. However, it only works well for around a third of patients, said the team from the Medical College of Georgia (MCG).
“Fibroblast cells” are the reason, they found.
“Collagen and many other proteins produced by these fibroblast cells accumulate outside of the vascular cells and eventually lead to fibrosis or scarring in the eye. This keeps the excess vasculature from being suppressed by anti-VEGF treatments,” revealed the study, published in the journal Science Translational Medicine.
“We show, for the first time in this study, that many fibroblast cells are actually produced by these excessive endothelial cells,” said Yuqing Huo, the Director of the Vascular Inflammation Programme at MCG’s Vascular Biology Center.
To prevent this from happening, the team targeted the adenosine receptor 2A (Adora2a) — a G-protein-coupled adenosine receptor found in high levels in the brain, immune cells, and blood vessels.
Although crucial in modulating inflammation, myocardial oxygen consumption, and coronary blood flow, in excess, adenosine can lead to excessive blood vessel growth.
Using genetically engineered mice that develop fibrosis in the backs of their eyes, the researchers delivered an Adora2a agonist (KW6002), which binds to the receptor and blocks its function. The mice demonstrated decreased fibrosis in the eye, the team said.
“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,” Huo said.
