ZIP2 and ZIP4 mediate age-related zinc fluxes across the retinal pigment epithelium

J Mol Neurosci. 2012 Jan;46(1):122-37. doi: 10.1007/s12031-011-9536-0. Epub 2011 May 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Aging / metabolism*
  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Cation Transport Proteins / antagonists & inhibitors
  • Cation Transport Proteins / biosynthesis
  • Cation Transport Proteins / physiology*
  • Cell Line
  • Child
  • Child, Preschool
  • Down-Regulation / physiology
  • Humans
  • Infant
  • Infant, Newborn
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Primary Cell Culture
  • Protein Transport / physiology
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology
  • Young Adult
  • Zinc / metabolism*

Substances

  • Cation Transport Proteins
  • SLC39A2 protein, human
  • SLC39A4 protein, human
  • Zinc