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J. Iacovelli, P. Veldman, P. Ojha, P. Hahn, A. Donovan, N. Andrews, J. L. Dunaief; The Iron Exporter Ferroportin Plays A Role in Retinal Iron Homeostasis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):214.
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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 (Fpn), 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 Fpn within the retina, we have generated a conditional knockout of Fpn in the RPE of mice.
Conditional knockout of Fpn 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 (Veldman et al., ARVO 2008). Retinas of VMD2-Cre positive, floxed Fpn progeny and controls were analyzed for retinal degeneration by fundus examination and histology and for iron overload by Ferritin Immunofluorescence (IF) and Perls’ histochemical stain. Transferrin Receptor (TfR) and Fpn immunofluorescence was also performed.
VMD2-Cre positive, floxed Fpn mice age 8 months show increased Ferritin staining within Cre positive RPE cells, suggesting elevated intracellular iron levels. Retinal iron levels from these mice are currently being tested by the Perls’ stain.
This initial characterization of conditional Fpn knockout mice suggests a role of Fpn 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 Fpn leads to retinal degeneration in aged mice
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