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Imre Lengyel, Peter A Kakalec, Erinn Gideon, Ryan Tappero, Jane Flinn; Correlation of trace metal distributions in sub-RPE deposits associated with age-related macular degeneration: an X-ray fluorescent study. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1332.
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The presence of several trace metals has been described in sub-RPE deposits and associated with the development and progression of age-related macular degeneration (AMD). In our present study we determined the correlation of the distribution and concentration of zinc, copper, iron, calcium in peripheral hard and macular soft drusen isolated from a human donor eye.
The donor eye with post mortem identified macular and peripheral drusen were obtained from the UCL Institute of Ophthalmology Eye Depository/Moorfields Eye Bank. The sample were obtained after research consent and appropriated ethics permission was obtained. Tenets of the Helsinki Declaration and the guidelines from ARVO were followed. Following the removal of the neuronal retina and the retinal pigment epithelial cells drusen were visualized by pre-labeling with a zinc selective fluorescent dye ZinPyr-1, isolated using a binocular fluorescent dissecting microscope (Nikon ZM1500) and 20 micron sections were cut on a cryostat. To determine trace metal levels brain sections spiked with pre-determined trace metal levels were used as standard sectioned as above. The sections were analyzed by microprobe synchrotron X-ray fluorescence at the X27A beam line at the National Synchrotron Light Source at Brookhaven National Laboratory. Results were analyzed using Excell.
24 individual sectioned hard drusen and two very large soft drusen were analysed. Pixel by pixel comparison of metal levels showed no significant correlation with each other. Zinc levels were within the same concentration range we reported earlier (>100 ppm). There are significantly lower concentrations of iron and, especially, copper in all drusen. However, calcium levels in both soft and hard drusen can reach the >1,000 ppm. Zinc and calcium were fund in all drusen but not all drusen contained iron and/or copper.
High concentrations of zinc and calcium were present in all drusen suggesting that their accumulation may play a role in the development and/or progression of sub-RPE deposit formation and, eventually, AMD. Iron and copper levels are low and variable in drusen. The exact role for trace element accumulation in the disease process, however, is yet to be determined.
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