Bmp6 regulates retinal iron homeostasis and has altered expression in age-related macular degeneration.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hadziahmetovic, M; Song, Y; Wolkow, N; Iacovelli, J; Kautz, L; Roth, M-P; Dunaief, JL

Published Date

  • July 2011

Published In

Volume / Issue

  • 179 / 1

Start / End Page

  • 335 - 348

PubMed ID

  • 21703414

Pubmed Central ID

  • 21703414

Electronic International Standard Serial Number (EISSN)

  • 1525-2191

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/j.ajpath.2011.03.033

Language

  • eng