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
Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal; Department of Morphology and Function, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal; Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal; Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.
PLoS One. 2014 Sep 26;9(9):e106974. doi: 10.1371/journal.pone.0106974. eCollection 2014.
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.
铁在视网膜中至关重要，因为含血红素的酶鸟苷酸环化酶可调节视杆细胞和视锥细胞中的光转导。转铁蛋白内吞作用是视网膜从血液循环中获取铁的经典途径。然而，铁储存蛋白铁蛋白最近也被认为是一种铁载体。在本研究中，我们调查了Scara5在视网膜中的存在及其与L-铁蛋白的结合情况。我们的结果表明，L-铁蛋白的特异性受体Scara5在小鼠和人类视网膜的多种细胞类型中表达，包括内皮细胞。此外，我们还表明，静脉注射的铁蛋白通过L-铁蛋白与内皮细胞中的Scara5结合穿过血视网膜屏障。因此，提示视网膜中存在一种新的铁传递和运输途径。在光感受器变性的小鼠模型中，Scara5表达下调，表明该受体可能参与视网膜病变，也是一个潜在的治疗靶点。
