In the retina, iron is particularly critical for the visual phototransduction cascade. In the retinal pigment epithelium (RPE), RPE65 activity leads to 11-cis-retinaldehyde, the photosensitive component of rhodopsin production and iron containing enzymes are necessary for disc replacement in photoreceptor cells. Iron is not excreted from the body and accumulates in tissues including the retina, a process that has been associated with age-related macular degeneration (AMD). Iron import into cells relies on two pathways, transferrin bound and non-transferrin bound processes. To address cellular iron transport two ceruloplasmin / hephaestin double knockout mice (CpHeph) and hepcidin knockout mice (Hep) which accumulate intracellular iron in an age dependent manner were used. The studies analysed the expression of three iron importers in these and wild type mice. The results show that two importers (Zip8 and Zip14) were expressed in the mouse retina and were upregulated in both KO strains compared to the wild-type animals. Both Zip8 and Zip14 protein levels were raised in Cp/Heph mice while only Zip8 levels were increased in the Hep mice. Levels of Zip14 could be modulated by intravitreal injection of transferrin. This data indicates that Zip8 and Zip14 are modulators of retinal iron accumulation via an increase in import of non-transferrin bound iron, that in a positive feedback loop prevent degradation of the importers, a process that may be relevant in AMD.

Iron importers Zip8 and Zip14 are expressed in retina and regulated by retinal iron levels.
Sterling J, Guttha S, Song Y, et al.
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Graham Wallace

Birmingham and Midland Eye Centre, Birmingham, UK.

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