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Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration

Metallomics

By:
, , , , and
https://doi.org/10.1039/c4mt00058g

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Abstract

Zinc (Zn) is abundantly enriched in sub-retinal pigment epithelial (RPE) deposits, the hallmarks of age-related macular degeneration (AMD), and is thought to play a role in the formation of these deposits. However, it is not known whether Zn is the only metal relevant for sub-RPE deposit formation. Because of their involvement in the pathogenesis of AMD, we determined the concentration and distribution of calcium (Ca), iron (Fe) and copper (Cu) and compared these with Zn in isolated and sectioned macular (MSD), equatorial (PHD) and far peripheral (FPD) sub-RPE deposits from an 86 year old donor eye with post mortem diagnosis of early AMD. The sections were mounted on Zn free microscopy slides and analyzed by microprobe synchrotron X-ray fluorescence (μSXRF). Metal concentrations were determined using spiked sectioned sheep brain matrix standards, prepared the same way as the samples. The heterogeneity of metal distributions was examined using pixel by pixel comparison. The orders of metal concentrations were Ca ⋙ Zn > Fe in all three types of deposits but Cu levels were not distinguishable from background values. Zinc and Ca were consistently present in all deposits but reached highest concentration in MSD. Iron was present in some but not all deposits and was especially enriched in FPD. Correlation analysis indicated considerable variation in metal distribution within and between sub-RPE deposits. The results suggest that Zn and Ca are the most likely contributors to deposit formation especially in MSD, the characteristic risk factor for the development of AMD in the human eye.

Additional publication details

Publication type:
Article
Publication Subtype:
Journal Article
Title:
Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration
Series title:
Metallomics
DOI:
10.1039/c4mt00058g
Volume:
6
Issue:
7
Year Published:
2014
Language:
English
Publisher:
Royal Society of Chemistry
Contributing office(s):
National Research Program - Eastern Branch
Description:
6 p.
First page:
1223
Last page:
1228