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Y. Song, M. Hadziahmetovic, A. Hunter, J. Iacovelli, N. Haddad, S. Vaulont, J. L. Dunaief; Peptide Hormone Hepcidin Regulates Retinal Iron Homeostasis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3504.
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Age related macular degeneration (AMD) is the leading cause of blindness in the elderly. Elevated iron levels in AMD retinas and early onset retinal degeneration in mice and humans with hereditary iron overload suggest that iron induced oxidative stress may exacerbate the disease. Studies on retinal iron regulation may explain how iron accumulates in the retina and suggest novel therapeutic modalities. The iron regulatory hormone hepcidin is secreted by the liver to regulate iron import in the intestine. Here, we test whether hepcidin, which is produced by the retina (Gnana-Prakasam, Biochemi J, 2008) may regulate retinal iron import.
Hepcidin knockout mouse retinas were studied by histology, immunohistochemistry, Perls’ stain for iron, atomic absorption spectrophotometry to quantify iron, and qPCR for iron regulatory genes. Hepcidin mRNA levels were also assessed by qPCR in mice with retinal iron overload resulting from mutation in ceruloplasmin and hephaestin or from iron injection into the eye. Hepcidin regulatory proteins ERK and SMAD were also assessed by Western analysis following intraocular iron injection.
Hepcidin knockout mice have age-dependent retinal iron accumulation and retinal degeneration with some features of AMD. Retinal hepcidin production was increased in mice with elevated retinal iron levels, following ERK phosphorylation. Retinal levels of hepcidin’s target, the iron exporting protein ferroportin, were increased in hepcidin knockouts and decreased when hepcidin was upregulated by iron injection into the eye.
Hepcidin regulates not just systemic iron levels but also functions locally to control retinal iron homeostasis. Upregulated by IL6, hepcidin may cause iron dysregulation in diseases involving retinal inflammation.
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