| First Author | Hadziahmetovic M | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 1 | Pages | 335-48 |
| PubMed ID | 21703414 | Mgi Jnum | J:174000 |
| Mgi Id | MGI:5050766 | Doi | 10.1016/j.ajpath.2011.03.033 |
| Citation | Hadziahmetovic M, et al. (2011) Bmp6 regulates retinal iron homeostasis and has altered expression in age-related macular degeneration. Am J Pathol 179(1):335-48 |
| abstractText | 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. |
