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AMD Linked To Calcium Deposits

New research into the underlying mechanisms of age-related macular degeneration is pointing to the build up of minute mineral deposits in the eye, suggesting that the condition could be triggered by similar compounds to those which give bone and teeth their strength.

It has long been established that accumulation of extracellular waste materials in the eye is part of the ageing process, and that the presence of this build up is strongly linked with AMD. Previous research had shown that trace metals, such as zinc, along with lipid and protein are present in these deposits under the retinal pigment epithelium (RPE). But a paper published this month by an international group of researchers has revealed a specific form of calcium phosphate, called hydroxyapatite (HAP), may play a crucial role in starting the process off.

HAP is a similar form of calcium to the composite found in bone and teeth; so finding it in deposits in the eye was a surprise. “We had no idea that HAP might be involved. That's what makes this work so exciting,” said lead author of the study and associate professor of biochemistry and molecular biology at the University of Maryland School of Medicine, Professor Richard Thompson, in a press statement. “It opens up a lot of new research opportunities.”

Using fluorescent staining and X-ray diffraction, Professor Thompson and colleagues in the US, UK and Germany, looked at a number of donor eyes and discovered tiny spheres of HAP underneath the RPE. The team believe that the spheres act as the initial binding site for proteins, which in turn leads to more and more binding of protein and lipids in a gradual snowball effect, forming larger globules of drusen over time.

Dr Lengyel, a senior research fellow at the UCL Institute of Ophthalmology, explained that at the heart of the spheres are lipid droplets containing cholesterol – which is regularly transported between the RPE and the bloodstream. “Something happens on the surface of these lipid droplets which allows the HAP to precipitate and then this whole process takes place, which may eventually lead to clinically relevant symptoms,” he told OT.  

“These HAP deposits would probably show you that something is going wrong before you see drusen in vivo,” added Dr Lengyel. While the mineral deposits are too small to see with an ophthalmoscope, their fluorescence signal can be boosted with dyes, making them visible. “If you can increase the signal, then we could potentially pick up the tiny signal which otherwise could not be seen by normal methods,” he said.

One of the dyes used in the research has similar characteristics to the commonly used indocyanine green (ICG), leading the team to believe that a direct clinical application is a real potential. Dr Lengyel points out that this is yet to be tested, and that the technique would be of limited diagnostic value – as deposits also appear in non-AMD patients – but it could offer an early warning system by tracking the changes to the size of the HAP spheres linked with the disease process.

He told OT: “That’s where the progression option is an interesting one, if you do see these [deposits] grow, we could potentially develop intervention strategies. We could interfere at such an early stage that these later steps, which lead to blindness, may not develop.”

The research is published in Proceedings of the National Academy of Sciences. (Taken from Optometry Today

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