Blood-retinal barrier serum ferritin transport in mouse retina

Purpose The general requirement for iron is due to its involvement in various heme and non-heme-containing enzymes, which are ubiquitously involved in metabolic pathways. Iron accumulation is associated with some degenerative diseases, and in the retina with several retinopathies. Iron transport and cell type involved in iron storage mechanisms in the retina are not completely understood. Methods The iron content was analysed by EDX. Retina ferritin, TIM2 and Scara5 receptors were studied by means of confocal microscopy, rt-PCR and WB. Horse spleen ferritin (HSF) was intravenously injected in healthy ICR mice and in a murine model of blood-retinal barrier (BRB) breakdown. Results EDX detected iron in perivascular cell lysosomes that significatively accumulate iron in comparison with other cellular compartments. In the lower pH of lysosomes iron is released from transferrin and transported to the cytoplasm. However, this mechanism cannot explain the referred iron lysosomal accumulation. Recently, ferritin was proposed as a new iron delivery protein. TIM2 and Scara5 receptors, that bind to H- and L-ferritin, were expressed in mouse retina, suggesting that serum ferritin can be transported across the BRB into the retinal parenchyma. HSF was intravenously injected and, as expected, ferritin crossed the BRB, probably through TIM2 and Scara5 receptor binding, and accumulated in perivascular cells. In the presence of BRB breakdown injected ferritin was also found accumulated in TIM2 and Scara5 positive cells. Conclusion Serum ferritin uptake could represent a new pathway of iron delivery in the retina and points out perivascular cells as a key element in retinal iron storage.