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

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....

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Bibliographic Details
Published in:Metallomics 2014-01, Vol.6 (7), p.1223-1228
Main Authors: Flinn, Jane M, Kakalec, Peter, Tappero, Ryan, Jones, Blair, Lengyel, Imre
Format: Article
Language:English
Subjects:
Aged, 80 and over
Animals
Calcium - metabolism
Copper - analysis
Humans
Iron - metabolism
Macular Degeneration - pathology
Macular Degeneration - physiopathology
Retinal Pigment Epithelium - chemistry
Sheep
Spectrometry, X-Ray Emission
Zinc - metabolism
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Summary: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.
ISSN:1756-5901
1756-591X
DOI:10.1039/c4mt00058g