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Liangliang Zhao, Yafeng Li, Delu Song, Ying Song, Milan Theurl, Joshua L Dunaief; Retinal iron accumulation despite an intact blood-retinal barrier in mice with high serum iron. Invest. Ophthalmol. Vis. Sci. 2014;55(13):402.
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The retina is shielded from potentially harmful blood components by the blood-retinal barrier. Since the retina is exquisitely sensitive to iron levels, it is important to understand the roles of systemic versus local influences on retinal iron levels. The peptide hormone hepcidin (Hepc), which, in turn, is regulated by Bmp6, is an important regulator of systemic iron metabolism, yet hepcidin’s role locally in the retina is incompletely understood.
Retinas of systemic bone morphogenic protein 6 (Bmp6) knockout (KO) mice were analyzed by Perls’ iron stain and immunofluorescence to assess the levels of iron and iron-regulated proteins. Levels of retinal and isolated RPE Hepc mRNA were measured by qPCR.
H-ferritin and L-ferritin immunoreactivity (which is directly correlated with iron levels) in the neural retina (NR) and retinal pigment epithelium (RPE) increased in male Bmp6 KO mice compared to age-matched WT males. Female Bmp6 KOs had significantly less retinal ferritin than Bmp6 KO males. Granular Perls’ iron stain was present in the RPE. Retinal Hepc mRNA levels increased in parallel with iron levels in Bmp6 KO. Hepc mRNA levels were not decreased in the NR or RPE at any age in Bmp6 KO mice.
These findings indicate that elevated serum iron levels resulting from systemic Bmp6 KO can overwhelm any local retinal iron regulatory mechanisms. While Hepc may play a local iron regulatory role in the retina, this is insufficient to prevent retinal iron overload in the face of markedly elevated serum iron levels. The retinal regulation of Hepc correlated with retinal iron status rather than being regulated by a local Bmp6 pathway.
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