Promising Science

Scientists Uncover New Clues About How Macular Degeneration Forms

Calcium crystals may play key role in onset of macular degeneration.

Thursday, July 2, 2015
Rendition of mineral, fat, and protein deposits in a cell.
Imre Lengyel
BrightFocus-funded researchers have proposed that drusen form around microscopic sphere-shaped mineral deposits (shown in pink), which then attract fat and protein deposits (shown in green).

An international research team has uncovered some clues to how age-related macular degeneration (AMD) begins, and their findings could lead to new avenues of research and early diagnosis.

BrightFocus-grantee Richard B. Thompson, PhD, of the University of Maryland, and co-investigator and senior author Imre Lengyel, PhD, of University College, London, have detailed how tiny spheres of mineralized calcium phosphate, called hydroxyapatite (HAP), may create the early “scaffolding” around which the hallmark drusen deposits of AMD form.

The presence of drusen is taken as a clinical sign of AMD, and used for diagnosis during a dilated eye exam. Once they reach a certain size, drusen may cause AMD by preventing essential nutrients from reaching the eye’s light-sensing cells (photoreceptors). Until now, scientists did not know how drusen formed and grew. 

Researchers See a Process Unfold

Thompson and Lengyel believe that the mineralized spheres they and numerous colleagues have discovered attract various fat and protein particles to the sphere surface, which then form drusen. Specifically, a shell made of HAP forms around naturally occurring lipid droplets, then protein and fat molecules form around that.

HAP is common in the body—found in the hard part of bones and teeth—but it had never before been identified in the sub-retinal pigmented epithelium (RPE) part of the eye.

The discovery of HAP involvement, published in the February 3 print edition of the Proceedings of the National Academy of Sciences, attracted a lot of science press attention. Thompson said in a University of Maryland press release, “We had no idea that HAP might be involved. That’s what makes this work so exciting.  It opens up a lot of new research opportunities.”     

How Heavy Metal Experts Unlocked a Mystery

In 2014, Thomson and Lengyel received a BrightFocus grant to study the role of zinc and HAP in inducing drusen formation. To do so, they had to produce images and measure tiny spheres of mineralized calcium. They did this through post-mortem exams of 30 eyes from donors ages 43 to 96 years old. “Eyes with more of these spheres contained more drusen,” says Lengyel.

The scientists hope that future research will find techniques to get to the crystalized spheres before the fat and protein build-up, to prevent further drusen growth. Researchers also found that some eye samples were coated with amyloid beta, which is linked to Alzheimer’s disease. Future techniques might also help in the early diagnosis of Alzheimer’s.

Marine Chemists Played a Role

Both scientists admit they are into “heavy metals.” Not the music, but how elemental metals aggregate in the body to influence health and disease. They acknowledge other scientists for their metal expertise.

Says Thompson of their methods to measure and develop imaging of metal ions, using fluorescent spectroscopy: “There’s some skill to doing these measurements. Most biochemists aren’t trained this way. We’ve been taught by guys like marine chemists—people who care about copper in the ocean. They’ve developed the techniques that we’ve adapted.”


This Promising Science article is excerpted from a longer article by BrightFocus Health and Science Writer Martha Taggart, For Fighting AMD, This Discovery ‘Rocks'.

The abstract of the Thompson and Lengyel study is here.

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