Abstract |
Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6(-/-) mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess.
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Authors | Majda Hadziahmetovic, Ying Song, Natalie Wolkow, Jared Iacovelli, Leon Kautz, Marie-Paule Roth, Joshua L Dunaief |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 179
Issue 1
Pg. 335-48
(Jul 2011)
ISSN: 1525-2191 [Electronic] United States |
PMID | 21703414
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Bmp6 protein, mouse
- Bone Morphogenetic Protein 6
- RNA, Messenger
- Iron
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Topics |
- Animals
- Blotting, Western
- Bone Morphogenetic Protein 6
(physiology)
- Cells, Cultured
- Enzyme-Linked Immunosorbent Assay
- Humans
- Iron
(metabolism)
- Iron Overload
- Macular Degeneration
(etiology, pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Oxidative Stress
- RNA, Messenger
(genetics)
- Retinal Degeneration
- Retinal Pigment Epithelium
(metabolism, pathology)
- Reverse Transcriptase Polymerase Chain Reaction
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