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: Delu Song, Levi N Kanu, Yafeng Li, Kristen L Kelly, Rupak K Bhuyan, Tomas Aleman, Jessica I W Morgan, Joshua L Dunaief
• Journal: Experimental eye research (Exp Eye Res) Vol. 151 Pg. 122-33 (10 2016) ISSN: 1096-0007 [Electronic] England
• PMID: 27565570 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Ferric Compounds
• Receptors, Transferrin
• Tfrc protein, mouse
• RNA
• Apoferritins
• Iron
• Ferric Oxide, Saccharated
• Glucaric Acid

Topics

• Animals
• Apoferritins (biosynthesis, genetics)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Ferric Compounds (administration & dosage, adverse effects)
• Ferric Oxide, Saccharated
• Gene Expression Regulation
• Glucaric Acid (administration & dosage, adverse effects)
• Injections, Intravenous
• Iron (metabolism)
• Macular Degeneration (chemically induced, genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• RNA (genetics)
• Real-Time Polymerase Chain Reaction
• Receptors, Transferrin (biosynthesis, genetics)
• Retinal Pigment Epithelium (drug effects, metabolism, pathology)