Journal
EXPERIMENTAL EYE RESEARCH
Volume 90, Issue 6, Pages 664-678Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2010.03.003
Keywords
iron homeostasis; retina; lens; ocular iron outfow; age-related macular degeneration; age-related cataracts; anemia of chronic inflammation; photoxidative damage
Categories
Funding
- NCRR NIH HHS [G12 RR003051-120037, G12 RR003051] Funding Source: Medline
- NIGMS NIH HHS [R25 GM061838, R25 GM061838-06] Funding Source: Medline
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This review is focused on iron metabolism in the retina and in the lens and its relation to their respective age-related pathologies, macular degeneration (AMD) and cataract (ARC). Several aspects of iron homeostasis are considered first in the retina and second in the lens, paying particular attention to the transport of iron through the blood-retinal barrier and through the lens epithelial cell barrier, to the immunochemistry of iron-related proteins and their expression in both the retina and the lens, and to the nature of the photochemical damage caused by UV light on both tissues. A comparative overview of some iron related parameters (total iron, transferrin (Tf), transferrin saturation and total iron binding capacity), in plasma and ocular tissues and fluids of three animal species is also presented. Based on results selected from the literature reviewed, and our own results, a scheme for the overall circulation of iron within and out of the eye is proposed, in which, (i) iron is pumped from the retina to the vitreous body by a ferroportin/ferroxidase-mediated process at the endfeet of Muller cells, (ii) vitreal Tf binds this iron and the complex diffuses towards the lens, (iii) the iron/Tf complex is incorporated into the lens extracellular space probably at the lens equator and moves to the epithelial-fiber interface, (iv) upon interaction with Tf receptors of the apical pole of lens epithelial cells, the iron/Tf complex is endocytosed and iron is exported as Fe3+ by a ferroportin/ferroxidase-mediated process taking place at the basal pole of the epithelial cells, and (v) Fe3+ is bound to aqueous humor Tf and drained with the aqueous humor into systemic blood circulation for recycling. The proposed scheme represents an example of close cooperation between the retina and the lens to maintain a constant flow of iron within the eye that provides an adequate supply of iron to ocular tissues and secures the systemic recycling of this element. It does not discount the existence of additional ways for iron to leave the eye through the blood-retinal barrier. In this review both AMD and ARC are recognized as multifactorial diseases with an important photoxidative component, and exhibiting a remarkable similitude of altered local iron metabolism. The epidemiological relationship between ARC and ferropenic anemia is explained on the basis that hepcidin, the hormone responsible for the anemia of chronic inflammation, could paradoxically cause intracellular iron overload in the lens by interfering with the proposed ferroportin/ferroxidase-mediated export of iron at the basal side of the anterior lens epithelium. Other authors have suggested that a similar situation is created in the retina in the case of AMD. (C) 2010 Elsevier Ltd. All rights reserved.
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