Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport
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Disease Models, Animal
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Endothelial Cells / metabolism
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Female
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Ferritins / blood
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Ferritins / genetics
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Ferritins / metabolism*
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Gene Expression
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Gene Expression Regulation
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Humans
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Iron / metabolism
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Male
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Mice
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Photoreceptor Cells / metabolism
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Photoreceptor Cells / pathology
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Protein Binding
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Protein Transport
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Retina / cytology
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Retina / metabolism
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Retina / pathology
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Retinal Degeneration / genetics
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Retinal Degeneration / metabolism
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Retinal Degeneration / pathology
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Retinal Diseases / metabolism
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Retinal Diseases / pathology
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Retinal Neurons / metabolism
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Scavenger Receptors, Class A / genetics
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Scavenger Receptors, Class A / metabolism*
Substances
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SCARA5 protein, human
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Scavenger Receptors, Class A
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Ferritins
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Iron
Grants and funding
This study was supported by grants from PTDC/SAU-ORG/110856/2009 from Fundação para a Ciência e a Tecnologia do Ministério da Educação e Ciência, Portugal and from Instituto de Salud Carlos III (PI12/00605), Ministerio de Ciencia e Innovacion, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.