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J. Iacovelli, M. Nassar, A. Schumacher, J. L. Dunaief; Retinal Degeneration in Polycythaemia Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4510.
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We have previously demonstrated increased iron levels in AMD-maculas and macular degeneration in a patient with aceruloplasminemia, an iron overload disease. Furthermore, aged mice lacking the ferroxidases Ceruloplasmin and Hephaestin develop iron overloaded, hypertrophic RPE suggesting that these ferroxidases along with the iron transport protein Ferroportin (Fpn) mediate retinal iron export. Recently, the mouse polycythaemia (Pcm) mutation, a microdeletion in the Fpn promoter region, has been shown to cause iron accumulation in tissues due to dysregulated Fpn expression. To help elucidate Fpn’s retinal function, we studied retinal morphology and iron homeostasis in Pcm mice.
Retinal plastic sections from Pcm homozygous and control wild-type mice on an A/J background were analyzed for retinal morphology. Immunofluorescence (IF) for Fpn and transferrin receptor (TfR) was conducted on retinal cryosections.
Pcm homozygotes had decreased photoreceptor nuclei per row compared to wild-type at 12 weeks and only 2-4 photoreceptor nuclei per row and loss of outer segments at 1 year of age. Fpn IF demonstrated increased Fpn levels in the outer plexiform layer and RPE at 7 weeks and 1 year of age compared to controls. TfR immunoreactivity was increased in photoreceptors from 7 week old Pcm homozygotes compared to age matched wildtype retinas.
Increased levels of Fpn in the RPE at 7 weeks may promote excessive retinal iron export causing low retinal iron levels. The increased TfR staining in Pcm homozygotes is consistent with this hypothesis, as TfR levels increase when intracellular labile iron levels decrease. Therefore, retinal iron deficiency may be the cause of the retinal degeneration in older Pcm homozygotes.
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