Iron importers Zip8 and Zip14 are expressed in retina and regulated by retinal iron levels.

Journal Article

Intracellular retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness among individuals over the age of 50. Ceruloplasmin/hephaestin double knockout mice (Cp/Heph DKO) and hepcidin knockout mice (Hepc KO) accumulate retinal iron and model some features of AMD. Two canonical pathways govern cellular iron import - transferrin-bound iron import and non-transferrin bound iron import. In Cp/Heph DKO and Hepc KO iron-loaded retinas, transferrin-bound iron import is downregulated. Despite this effort to reduce cellular iron burden, iron continues to accumulate in these retinas in an age-dependent manner. Quantitative RT-PCR and Western analysis were used to quantify the expression of three ferrous iron importers, Dmt1, Zip8, and Zip14, in wild-type (Wt), Cp/Heph DKO, and Hepc KO retinas. Zip8 and Zip14 protein levels were analyzed using Western analysis in mice injected intravitreally with either apo- or holo-transferrin to elucidate one possible mechanism of Zip14 regulation in the retina. Both zip8 and zip14 were expressed in the mouse retina. Paradoxically, protein levels of non-transferrin bound iron importers were upregulated in both Cp/Heph DKO and Hepc KO retinas. Intravitreal holo-transferrin injection decreased Zip 14 protein levels. These data indicate that Zip8 and Zip14 may take up increasing amounts of non-transferrin bound iron in these two mouse models of retinal iron accumulation. Their upregulation in these already iron-loaded retinas suggests a vicious cycle leading to toxicity.

Full Text

Duke Authors

Cited Authors

  • Sterling, J; Guttha, S; Song, Y; Song, D; Hadziahmetovic, M; Dunaief, JL

Published Date

  • February 2017

Published In

Volume / Issue

  • 155 /

Start / End Page

  • 15 - 23

PubMed ID

  • 28057442

Electronic International Standard Serial Number (EISSN)

  • 1096-0007

International Standard Serial Number (ISSN)

  • 0014-4835

Digital Object Identifier (DOI)

  • 10.1016/j.exer.2016.12.008

Language

  • eng