Scara5 involvement in retinal iron metabolism

Purpose Although transferrin is the principal source of iron in mammalian cells, recently, ferritin was proposed as a new iron transporter protein. Serum ferritin is composed mostly, but not exclusively, of L‐ferritin, and in the presence of even a single H‐ferritin chain, up to 4500 atoms of iron can be incorporated into one ferritin molecule. As each transferrin molecule only binds to two iron atoms, serum ferritin can be regarded as a potential deliverer of a considerable large amount of iron to tissues. Iron implication in oxidative damage has become clear, and it is well known that iron accumulation is associated in the retina with several retinopathies. Methods Scara5 and L‐ferritin expression in the retina were studied by means of laser confocal microscopy, rt‐PCR and Western Blotting in ICR adult mice and in a murine model of retinopathy. Horse spleen ferritin was intravenously injected in healthy ICR adult mice and alteration in iron handling proteins expression was analyzed. Results Scara5 receptors, that specifically bind to L‐ferritin, were found in retinal endothelial and perivascular cells. Intravenous injected ferritin crossed the blood‐retinal barrier (BRB), through Scara5 receptor binding, and accumulated in these cells, suggesting that serum ferritin, mostly composed by L‐ferritin, can be transported across the BRB into the retinal parenchyma. During retinopathy, alterations in L‐ferritin levels and Scara5 expression were evaluated. Conclusion Serum ferritin uptake could represent a new pathway of iron delivery to the retina and points out perivascular cells as a key element in retinal iron traffic and during retinal iron accumulation associated with some retinopathies.