L-ferritin binding to scara5: a new iron traffic pathway potentially implicated in retinopathy

• Published in: PloS one Vol. 9; no. 9; p. e106974
• Main Authors: Mendes-Jorge, Luísa, Ramos, David, Valença, Andreia, López-Luppo, Mariana, Pires, Virgínia Maria Rico, Catita, Joana, Nacher, Victor, Navarro, Marc, Carretero, Ana, Rodriguez-Baeza, Alfonso, Ruberte, Jesús
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.09.2014; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Binding; Biological Transport; Biology and Life Sciences; Biotechnology; Blood; Blood circulation; Classical pathway; Cones; Degeneration; Diabetic retinopathy; Disease Models, Animal; Endocytosis; Endothelial cells; Endothelial Cells - metabolism; Female; Ferritin; Ferritins - blood; Ferritins - genetics; Ferritins - metabolism; Gene Expression; Gene Expression Regulation; Gene therapy; Guanylate cyclase; Heme; Humans; Interdisciplinary aspects; Iron; Iron - metabolism; Male; Medicine and Health Sciences; Mice; Photoreceptor Cells - metabolism; Photoreceptor Cells - pathology; Photoreceptors; Phototransduction; Protein Binding; Protein Transport; Proteins; Research and Analysis Methods; Retina; Retina - cytology; Retina - metabolism; Retina - pathology; Retinal degeneration; Retinal Degeneration - genetics; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Diseases - metabolism; Retinal Diseases - pathology; Retinal Neurons - metabolism; Retinopathy; Rods; Scavenger Receptors, Class A - genetics; Scavenger Receptors, Class A - metabolism; Smooth muscle; Transferrin; Transferrins; Veterinary colleges; Veterinary medicine; Portugal; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106974

Iron is essential in the retina because the heme-containing enzyme guanylate cyclase modulates phototransduction in rods and cones. Transferrin endocytosis is the classical pathway for obtaining iron from the blood circulation in the retina. However, the iron storage protein ferritin has been also recently proposed as an iron carrier. In this study, the presence of Scara5 and its binding to L-ferritin was investigated in the retina. Our results showed that Scara5, the specific receptor for L-ferritin, was expressed in mouse and human retinas in many cell types, including endothelial cells. Furthermore, we showed that intravenously injected ferritin crossed the blood retinal barrier through L-ferritin binding to Scara5 in endothelial cells. Thus, suggesting the existence of a new pathway for iron delivery and trafficking in the retina. In a murine model of photoreceptor degeneration, Scara5 was downregulated, pointing out this receptor as a potential player implicated in retinopathy and also as a possible therapeutic target.