Mice with hepcidin-resistant ferroportin accumulate iron in the retina.
FASEB J
; 30(2): 813-23, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26506980
ABSTRACT
Because ferroportin (Fpn) is the only known mammalian cellular iron exporter, understanding its localization and regulation within the retina would shed light on the direction of retinal iron flux. The hormone hepcidin may regulate retinal Fpn, as it triggers Fpn degradation in the gut. Immunofluorescence was used to label Fpn in retinas of mice with 4 different genotypes (wild type; Fpn C326S, a hepcidin-resistant Fpn; hepcidin knockout; and ceruloplasmin/hephaestin double knockout). No significant difference in Fpn levels was observed in these retinas. Fpn localized to the abluminal side of the outer plexiform vascular endothelial cells, Müller glia cells, and the basolateral side of the retinal pigment epithelium. Adeno-associated virus (AAV)-hepcidin was injected into the eyes of hepcidin knockout mice, while AAV-lacZ was injected into the contralateral eyes as a control. AAV-hepcidin injected eyes had increased ferritin immunolabeling in retinal vascular endothelial cells. Fpn C326S mice had systemic iron overload compared to wild type and had the fastest retinal iron accumulation of any hereditary model studied to date. The results suggest that physiologic hepcidin levels are insufficient to alter Fpn levels within the retinal pigment epithelium and Müller cells, but may limit iron transport into the retina from vascular endothelial cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte de Cátions
/
Epitélio Pigmentado da Retina
/
Hepcidinas
/
Ferro
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article