New Research: Tiny Calcium Deposits in the Eye May Trigger the Development of Macular Degeneration

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Researchers from the United States, the United Kingdom, and Germany have discovered that tiny spheres of calcium phosphate, a component of teeth and bones in the human body, may also provide a significant early triggering mechanism for the development of age-related macular degeneration (AMD).

The research team is investigating the possibility of using the presence of these calcium spheres as an early warning signal for AMD risk that can help with earlier intervention and diagnosis. According to the study authors, this finding “could potentially advance AMD diagnoses by at least a decade,” although “the road ahead is still long.”

From Proceedings of the National Academy of Sciences

The research, entitled Identification of hydroxyapatite spherules [i.e., tiny bone mineral spheres] provides new insight into subretinal pigment epithelial deposit formation in the aging eye (all explained below) has been published in the January 20, 2015 Early Edition of Proceedings of the National Academy of Sciences. Proceedings, first published in 1915, is the official journal of the National Academy of Sciences of the United States. It publishes research reports, commentaries, and reviews that span the biological, physical, and social sciences.

The authors are Richard B. Thompson, Valentina Reffatto, Jacob G. Bundy, Elod Kortvely, Jane M. Flinn, Antonio Lanzirotti, Emrys A. Jones, David S. McPhail, Sarah Fearn, Karsten Boldt, Marius Ueffing, Savanjeet Guy Singh Ratu, Laurenz Pauleikhoff, Alan C. Bird, and Imre Lengyel, who represent the following institutions: the University of Maryland School of Medicine; University College London; Imperial College London; University of Tübingen, Germany; George Mason University, Fairfax, VA; and The University of Chicago, IL.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. It is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD. Approximately 85-90% of affected persons have the “dry” type of AMD; 10-15% have the “wet” type.

Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 85-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. “Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss; they are, however, a risk factor for progressing to vision loss.

Wet (Neovascular) Macular Degeneration

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

About the Research

Excerpted from Calcium deposits may trigger degenerative blindness, via redOrbit:

Age-related macular degeneration (AMD) may be caused by deposits of microscopic calcium phosphate spheres in the eye. In the study, [the researchers] note that this is the first time these mineralized calcium phosphate spheres have been implicated in AMD. The possible involvement of these tiny calcium spheres, also known as hydroxyapatite (HAP), could ultimately lead to early detection of the disease.

As the researchers explain, HAP is common in the body. It makes up the hard part of teeth and bones, but it had never been detected in the retinal samples of elderly patients. This discovery could help scientists learn how AMD develops, as well as how to better diagnose and treat the condition.

AMD is characterized by a build-up of drusen (deposits of fat and protein) in the retina, which prevents essential nutrients from reaching light-sensitive cells called photoreceptors. Photoreceptors are regularly recycled by cellular processes, which create waste products. Drusen can trap this material, however, causing it to build up in the retina.

Previously, scientists did not fully understand how drusen formed and grew to clinically relevant size, but the new study shows that HAP particles could be responsible. The study authors believe that the calcium spheres could attract proteins and fats to the surface, causing them to accumulate over the course of several years or even decades to form drusen.

The researchers made their discovery through post-mortem examination of 30 eyes from donors between 43 and 96 years old. Using fluorescent dyes, they were able to identify the miniature calcium spheres. They also examined tissue samples from AMD patients using X-ray diffraction and fluorescent staining chemicals, which helped reveal the role of HAP in the process.

“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 lead investigator Dr. Imre Lengyel. “Eyes with more of these spheres contained more drusen.”

Dr. Lengyel noted that the spheres appear long before the drusen itself becomes visible during a clinical examination, and that the new techniques can be used to identify drusen buildup long before it becomes visible using current techniques. The findings could potentially advance AMD diagnoses by at least a decade, she added.

More about the Study from Proceedings of the National Academy of Sciences

From the article abstract:

Significance: Proteins and lipids accumulating in deposits external to the retinal pigment epithelium (RPE) represent a barrier to metabolic exchange between the retina and the choroidal capillaries. With time, these deposits can lead to age-related macular degeneration (AMD), the most common cause of blindness in the elderly in the developed world.

[Editor’s note: The retinal pigment epithelium (RPE) is a specialized retinal tissue that plays a crucial role in maintaining the equilibrium of all retinal processes. It is the pigmented layer of the retina, containing the deepest cells of the retina. The choroid is a dark brown membrane that is rich with blood vessels. It supplies blood and nutrients to the retina and nourishes all of the other structures within the eye.]

It remains unclear how sub-RPE deposits are initiated and grow to clinically relevant features. Using a combination of high-resolution analytical techniques, we found that tiny hydroxyapatite (bone mineral) spherules with cholesterol-containing cores are present in all examined sub-RPE deposits, providing a scaffold to which proteins adhere.

If the spherules are important in initiating sub-RPE deposit formation, this finding may provide attractive new approaches for early identification and treatment of AMD.

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