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.
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