June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A mineralomic study of the retinal pigment epithelium-Bruch’s membrane complex in human eyes with age-related macular degeneration
Author Affiliations & Notes
  • Matthew Pilgrim
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
    Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, London, United Kingdom
  • Anna CS Tan
    Singapore National Eye Centre, Singapore, Singapore, Singapore
    Singapore Eye Research Institute, Singapore, Singapore, Singapore
  • Sarah Fearn
    Department of Materials, Imperial College London, London, United Kingdom
  • Elena Tsolaki
    Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
  • Sergio Bertazzo
    Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
  • Imre Lengyel
    Centre for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
  • Christine Curcio
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Matthew Pilgrim, None; Anna Tan, Bayer (R), Zeiss (R); Sarah Fearn, None; Elena Tsolaki, None; Sergio Bertazzo, None; Imre Lengyel, Optos (F), University College London (P); Christine Curcio, Hoffman La Roche (F), Novartis (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2266. doi:
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      Matthew Pilgrim, Anna CS Tan, Sarah Fearn, Elena Tsolaki, Sergio Bertazzo, Imre Lengyel, Christine Curcio; A mineralomic study of the retinal pigment epithelium-Bruch’s membrane complex in human eyes with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2266.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Clinical and histological imaging has suggested the existence of 3 distinct, potentially mineralized deposits in the retinal pigment epithelium (RPE)-Bruch’s membrane (BrM) complex in human eyes with age-related macular degeneration (AMD): spherules, BrM plaques and large nodules. Whilst the elemental composition and mineral form of spherules (PMID 25605911), and to a lesser extent plaques (PMID 1543459), has been investigated, the elemental composition and mineral content of nodules remains undetermined (PMID 9620067). This study aims to identify the mineral components of plaques and nodules and compare them to the calcium (Ca) and phosphate (P) spherules previously observed in human drusen.

Methods : Human cadaveric eyes meeting histologic criteria for AMD were dissected and embedded in epoxy resin or paraffin wax, sectioned at 2 μm or 4 to 8 µm respectively, and mounted on to glass slides or on to Ultralene when appropriate. The elemental composition of BrM plaques and nodules was investigated using density dependent-scanning electron microscopy (DDC-SEM), energy dispersive x-ray spectroscopy (EDX), secondary ion mass spectroscopy (SIMS), and synchrotron micro-focus x-ray fluorescence (µXRF). Mineral components were determined using transmission electron microscopy-selected area electron diffraction (TEM-SAED).

Results : Using DDC-SEM, spherules, BrM plaques, and nodules were shown to contain dense material suggestive of mineralization. All 3 of these features were shown to contain Ca and P by EDX and SIMS: spherules (eyes, n=3), BrM plaques (eyes, n=3) and nodules (eyes, n=3). TEM-SAED confirmed that all types of mineralized deposits were composed of apatite.

Conclusions : Ca and P were detected in all types of mineralized deposit, spherules, BrM plaques and, importantly, for the first time in large nodules. Identification of Ca and P and the mineral forms in each deposit type, along with our prior demonstration of apatite in RPE cell cultures (ARVO 2016), highlights the need for further research on Ca and P homeostasis in the RPE-BrM complex. Better understanding of this aspect of RPE physiology can aid the development of novel therapeutic interventions for AMD. Furthermore, mineralization is readily observed using multimodal clinical imaging; therefore these data can also help improve clinical image interpretation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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