Flinn Jane M, Kakalec Peter, Tappero Ryan, Jones Blair, Lengyel Imre
Psychology, George Mason University, Fairfax, VA, USA.
Metallomics. 2014 Jul;6(7):1223-8. doi: 10.1039/c4mt00058g.
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.
锌（Zn）在视网膜色素上皮（RPE）下沉积物中大量富集，而RPE下沉积物是年龄相关性黄斑变性（AMD）的标志，并且被认为在这些沉积物的形成中起作用。然而，尚不清楚锌是否是与RPE下沉积物形成相关的唯一金属。由于它们参与了AMD的发病机制，我们测定了钙（Ca）、铁（Fe）和铜（Cu）的浓度和分布，并将其与来自一名86岁供体眼的分离和切片的黄斑（MSD）、赤道（PHD）和远周边（FPD）RPE下沉积物中的锌进行比较，该供体眼经尸检诊断为早期AMD。将切片安装在无锌显微镜载玻片上，并通过微探针同步加速器X射线荧光（μSXRF）进行分析。使用加标切片羊脑基质标准物测定金属浓度，其制备方法与样品相同。通过逐像素比较来检查金属分布的异质性。在所有三种类型的沉积物中，金属浓度的顺序为Ca ⋙ Zn > Fe，但铜水平与背景值无法区分。锌和钙始终存在于所有沉积物中，但在MSD中浓度最高。铁存在于一些但不是所有的沉积物中，并且在FPD中特别富集。相关性分析表明，RPE下沉积物内部和之间的金属分布存在相当大的差异。结果表明，锌和钙最有可能促成沉积物的形成，尤其是在MSD中，而MSD是人类眼中AMD发展的特征性风险因素。
