title: AMD-like retinopathy associated with intravenous iron.
abstract: Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (-Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls' iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch's membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas of high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch's membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment.
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Delu
authors: D
authors: Song
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Levi N
authors: LN
authors: Kanu
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Yafeng
authors: Y
authors: Li
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Kristen L
authors: KL
authors: Kelly
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Rupak K
authors: RK
authors: Bhuyan
authors: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Tomas
authors: T
authors: Aleman
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors: Jessica I W
authors: JI
authors: Morgan
authors: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: jdunaief@mail.med.upenn.edu.
authors: Joshua L
authors: JL
authors: Dunaief
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077605:Ferric Oxide, Saccharated; D005786:Gene Expression Regulation; D005937:Glucaric Acid / Q000008:administration & dosage / Q000009:adverse effects*; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism*; D008268:Macular Degeneration / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D005290:Ferric Compounds; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D012313:RNA; D001052:Apoferritins; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
keywords: AMD; Iron; Macular degeneration; Oxidative stress; RPE