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Noel Casey, Juliet A. Moncaster, Olga Minaeva, Mark W. Wojnarowicz, Amanda Gaudreau, Srikant Sarangi, Francis Doyle, Lee E. Goldstein; Metallomic Imaging Optical and Mass Spectrometry Mapping of the Murine and Human Eye in Normal Aging and Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3030.
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We have previously identified amyloid-beta deposition, amyloid pathology, and co-localizing supranuclear cataracts in Alzheimer’s disease (AD) and Down Syndrome (DS) subjects (Goldstein, Lancet, 2003, Moncaster, Plos One, 2010). Metal-mediated A-Beta aggregation in brain and lens is a major contributor to AD pathogenesis, the basis for a therapeutic strategy (Lannfelt, Lancet Neurol., 2008) and underpins our development of a non-invasive laser diagnostic for AD based on quasi-elastic light scattering. To further understand metal homeostasis in AD pathogenesis, we utilized Metallomic Imaging Mass and Optical Spectrometry (MIMOS) to perform high-resolution metallomic mapping of the brain and eyes from AD transgenic mice and age-matched wild-type controls and from human subjects with AD and age-matched non-AD controls.
Human eyes and brains were procured through the NIH-funded Boston University Alzheimer’s Disease Center brain bank and from NDRI (Philadelphia, PA). Eyes were flash frozen and analyzed by nanosecond laser ablation and magnetic sector field ICP-MS at the Boston University Center for Biometals and Metallomics (CBM). Laser ablation: wavelength, 213 nm; rate, 5-50 μ ms-1; spot size, 25 micron (scanning) to 3 micron (high-resolution). MIMOS analysis was conducted on surround to establish elemental background. Analytical calibration utilized NIST standards.
High-resolution metallomic maps generated from AD and age-matched control eyes in murine and human ocular tissue generated quantitative and reproducible elemental and isotopic distribution patterns. Zinc was confirmed in the subequatorial supranucleus of the lens, the same region implicated in AD-linked A-Beta accumulation and cataractogenesis. Retinal zinc demonstrated a laminar distribution corresponding to cytoarchitectonic organization. Retinal iron revealed a vascular distribution. The trabecular meshwork demonstrated high levels of zinc, copper, and iron. These findings are consistent with our previous low-resolution analyses by X-ray fluorescence microscopy.
MIMOS analysis generated detailed quantitative spatial distribution maps of essential and trace elements in adult human eyes at 5-25 micron spatial resolution. This study confirms a role for zinc as a pathogenic contributor to AD-linked pathology in the lens and brain.
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