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J. Iacovelli, P. Ojha, K. Gollomp, P. Hahn, A. Donovan, N. Andrews, J.L. Dunaief; The Iron Exporter Ferroportin Plays A Role In Retinal Iron Homeostasis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4157.
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© ARVO (1962-2015); The Authors (2016-present)
Iron can cause oxidative stress and elevated levels are associated with several neurodegenerative diseases. We have previously demonstrated increased iron levels in AMD–maculas and macular degeneration in a patient with aceruloplasminemia, an iron overload disease. Mice lacking the ferroxidases Ceruloplasmin (Cp) and Hephaestin (Heph) accumulate iron within the retina and develop retinal degeneration with features of AMD. Ferroportin (Fp), an iron transport protein, functions with Cp/Heph to transport iron out of cells. To study the role of iron accumulation in retinal degeneration and the function of Fp within the retina, we have generated a conditional knockout of Fp in the RPE of mice.
Fp protein was localized within the retina by immunohistochemistry (IHC) and Western analysis. Conditional knockout of Fp was generated within the mouse RPE using the Cre–LoxP system. RPE–specific Cre expression was obtained with a new VMD2–Cre transgenic mouse line (Gollomp et al., ARVO 2006). Retinas of VMD2–Cre positive, floxed Fp progeny and controls were analyzed for retinal degeneration by fundus examination and histology and for iron overload by Ferritin IHC and Perls’ stain.
Fp protein is present in the RPE and photoreceptors in the mouse retina and in the ARPE–19 cell line. VMD2–Cre positive, floxed Fp mice age 3, 4.5, and 6 months show increased Ferritin staining within Cre positive RPE nuclei, suggesting elevated intracellular iron levels. Retinal iron levels from these mice are currently being tested by the Perls’ stain.
This initial characterization of conditional Fp knockout mice suggests a role of Fp within the RPE in maintaining retinal iron homeostatsis. The mouse model presented herein along with our Cp/Heph knockout mice, provide evidence that iron export from the RPE is essential in maintaining retinal iron homeostasis. Ongoing studies will determine whether loss of Fp leads to retinal degeneration.
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