gms | German Medical Science

7th International Symposium on AMD: Age-related Macular Degeneration – Understanding Pathogenetic Mechanisms of Disease

20.09. - 21.09.2019, Baden-Baden

Is mineralization a major factor in drusen pathogenesis?

Meeting Abstract

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  • Imre Lengyel - Belfast/IRL

7th International Symposium on AMD: Age-related Macular Degeneration - Understanding Pathogenetic Mechanisms of Disease. Baden-Baden, 20.-21.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2020. Doc19amd12

doi: 10.3205/19amd12, urn:nbn:de:0183-19amd122

Published: February 5, 2020

© 2020 Lengyel.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

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Purpose: Drusen are a defining feature of the ageing eye and it is associated with age-related macular degeneration (AMD), a common sight-threatening disease of older adults. With an odds ratio of >7 large drusen is a significant risk factor for progression to advanced AMD, still, the molecular mechanism behind this increased risk was largely unknown. We recently proposed that calcium and phosphate containing minerals are key in this process and identified the mineral components of Bruch’s membrane (BrM) calcification as well large “calcified” nodules and compare these to the previously reported hydroxyapatite spherules.

Methods: Human cadaveric eyes were dissected and embedded in epoxy resin, sectioned at 0.5 to 2 μm and mounted on to glass slides or on to ultralene when appropriate. The elemental composition of BrM plaques and large calcified nodules was investigated using density dependent-scanning electron microscopy (DDC-SEM), energy dispersive x-ray spectroscopy (EDX), secondary ion mass spectroscopy (SIMS), and synchrotron microfocus x-ray fluorescence (µXRF). The mineral components were determined using transmission electron microscopy-selected area electron diffraction (TEM-SAED).

Results: Using DDC-SEM, spherules, BrM plaques and large calcified nodules were shown to contain dense material, later show to contain Ca and P by EDX and SIMS: spherules (spherules, n=100), BrM plaques (eyes, n=3) and calcified nodules (eyes, n=3). TEM-SAED confirmed that all 3 calcifications were composed of apatite.

Conclusions: We found calcium and phosphate in all types of calcific lesion: spherules, Bruch’s membrane plaques and large calcified nodules. However, differences in crystal structure and composition of the developing form, shape and size of apatite can be affected by the environment they are deposited in. These Results highlight the need for further research on calcium and phosphate homeostasis at the RPE-Choroid complex. Understanding these processes may aid the development of novel therapeutic interventions that target the progression of early-stage lesions to advanced stages of AMD.