Department of Neural and Behavioral Sciences, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
J Mol Neurosci. 2012 Jan;46(1):122-37. doi: 10.1007/s12031-011-9536-0. Epub 2011 May 21.
Decreases in systemic and cellular levels of zinc (Zn(2+)) during normal aging correlate with several age-related pathologies including age-related macular degeneration. Zn(2+) homeostasis in tissues is not only dependent on dietary intake but also on optimal expression and function of its influx (ZIP) and efflux (ZnT) transporters. We recently showed that many of the Zn(2+) transporters are expressed by the retinal pigment epithelial (RPE) cells. In this study, we present evidence that RPE cells contain less endogenous Zn(2+) with increased aging and transport this ion vectorially with greater transport from the basal to apical direction. Expression of two Zn(2+) influx transporters, ZIP2 and ZIP4, is reduced as a function of RPE age. Gene silencing of ZIP2 and ZIP4 in RPE cells from young donors or their overexpression in cells from older donors confirms that these two transporters are essential in controlling Zn(2+) influx and sequestration in RPE cells. Both transporters are distributed on the basal surface of the RPE where they are likely to control Zn(2+) homeostasis in the outer retina.
在正常衰老过程中，系统和细胞水平的锌（Zn(2+)）减少与几种与年龄相关的病理学有关，包括与年龄相关的黄斑变性。组织中的 Zn(2+)稳态不仅依赖于饮食摄入，还依赖于其流入（ZIP）和流出（ZnT）转运体的最佳表达和功能。我们最近表明，许多 Zn(2+)转运体由视网膜色素上皮（RPE）细胞表达。在这项研究中，我们提供的证据表明，随着年龄的增长，RPE 细胞内的内源性 Zn(2+)减少，并且从基底到顶侧方向以更大的向量运输这种离子。作为 RPE 年龄的函数，两种 Zn(2+)流入转运体 ZIP2 和 ZIP4 的表达减少。年轻供体的 RPE 细胞中的 ZIP2 和 ZIP4 基因沉默或年老供体的细胞中的过表达证实，这两种转运体对于控制 RPE 细胞中的 Zn(2+)内流和螯合至关重要。这两种转运体都分布在 RPE 的基底表面，它们可能控制外视网膜的 Zn(2+)稳态。
