AMD affects 1 in 5 people over 75, causing their vision to slowly
deteriorate, but the cause of the most common form of the disease remains a
mystery.* The ability to spot the disease early and reliably halt its
progression would improve the lives of millions, but this is simply not
possible with current knowledge and techniques.
The latest research, published in Proceedings
of the National Academy of Sciences, has implicated tiny spheres of
mineralised calcium phosphate, ‘hydroxylapatite’, in AMD progression. This not
only offers a possible explanation for how AMD develops, but also opens up new
ways to diagnose and treat the disease.
AMD is characterised by a build-up of mainly protein and fat containing
deposits called ‘drusen’ in the retina, which can prevent essential nutrients
from reaching the eye’s light-sensitive cells, ‘photoreceptors’. Photoreceptors
are regularly recycled by cellular processes, creating waste products, but drusen
can trap this ‘junk’ inside the retina, worsening the build-up. Until now,
nobody understood how drusen formed and grew to clinically relevant size.
The
new study shows that tiny calcium-based hydroxyapatite, commonly
found in bones and teeth, could explain the origin of drusen. The
researchers
believe that these spheres attract proteins and fats to their surface,
which
build up over years to form drusen. Through post-mortem examination of
30 eyes
from donors between 43 and 96 years old, the researchers used
fluorescent dyes
to identify the tiny spheres, just a few microns – thousandths of a
millimetre
– across.“We found these miniscule hollow spheres inside all of the eyes and all the deposits that we examined, from donors with and without AMD,” explains Dr Imre Lengyel, Senior Research Fellow at the UCL Institute of Ophthalmology and Honorary Research Fellow at Moorfields Eye Hospital, who led the study. “Eyes with more of these spheres contained more drusen. The spheres appear long before drusen become visible on clinical examination.
“The fluorescent labelling technique that we used can identify the early
signs of drusen build-up long before they become visible with current methods.
The dyes that we used should be compatible with existing diagnostic machines.
If we could develop a safe way of getting these dyes into the eye, we could
advance AMD diagnoses by a decade or more and could follow early progression
more precisely.”
Some of the mineral spheres identified in the eye samples were coated
with amyloid beta, which is linked to Alzheimer’s disease. If a technique were developed
to identify these spheres for AMD diagnosis, it may also aid early diagnosis of
Alzheimer’s. Whether these spheres are a cause or symptom of AMD is still
unclear, but their diagnostic value is significant either way. As drusen are hallmarks
of AMD, then strategies to prevent build-up could potentially stop AMD from
developing altogether.
“The calcium-based spheres are made up of the same compound that gives
teeth and bone their strength, so removal may not be an option,” says Dr
Lengyel. “However, if we could get to the spheres before the fat and protein
build-up, we could prevent further growth. This can already be done in the lab,
but much more work is needed before this could be translated into patients.”
“Our discovery opens up an exciting new avenue of scientific research
into potential new diagnostics and treatments, but this is only the beginning
of a long road.” says Dr Richard Thompson, the main international collaborator
from the University of Maryland School of Medicine, USA.
The work was supported by the Bill Brown Charitable Trust, Moorfields Eye
Hospital, Mercer Fund from Fight for Sight, and the Bright Focus Foundation.
The UCL-led international collaboration involved researchers from the
University of Maryland School of Medicine, Imperial College London, the University
of Tübingen, George Mason University, Fairfax, and the University of Chicago.