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1.
Exp Eye Res ; 151: 122-33, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27565570

RESUMO

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.


Assuntos
Compostos Férricos/efeitos adversos , Ácido Glucárico/efeitos adversos , Ferro/metabolismo , Degeneração Macular/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Animais , Apoferritinas/biossíntese , Apoferritinas/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado , Regulação da Expressão Gênica , Ácido Glucárico/administração & dosagem , Injeções Intravenosas , Degeneração Macular/genética , Degeneração Macular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores da Transferrina/biossíntese , Receptores da Transferrina/genética , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo
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