title: A high serum iron level causes mouse retinal iron accumulation despite an intact blood-retinal barrier.
abstract: The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms.
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China; F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Delu
authors.initials: D
authors.lastname: Song
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Milan
authors.initials: M
authors.lastname: Theurl
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China; F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Cwanger
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
authors.forename: Guanfang
authors.initials: G
authors.lastname: Su
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: jdunaief@upenn.edu.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D012160:Retina / Q000378:metabolism*
chemical_list: D055418:Bone Morphogenetic Protein 6; D064451:Hepcidins; D007501:Iron