title: Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy.
abstract: Despite the advance in medical technology, diabetic retinopathy (DR) is still an intractable disease which leads to the damage of retinal cells and finally the visual loss. Impairment of retinal vascular barrier triggered by an admixture of multiple inflammatory cytokines is a core of pathophysiology of DR. Therefore, the molecules involved commonly in multiple cytokines-induced impairment of vascular barrier would be the targets of curative treatment of DR. Here, we demonstrate that basigin, a transmembrane molecule expressed in neural barrier-forming endothelial cells, is the molecule essential for vascular barrier impairment which is shared by various triggers including VEGF, TNFα and IL-1β. In vitro data with neural microvascular endothelial cells indicated that stimulation with cytokines decreases the levels of claudin-5 in cell membranes and consequently impairs the barrier function in a manner dependent on the interaction of claudin-5 with basigin and caveolin-1. In addition, the increased vascular permeability in retinas of streptozotocin-induced diabetic mice was shown to be clearly normalized by intravitreous injection of siRNAs specific for basigin. This study has highlighted basigin as a common essential molecule for various stimuli-induced impairment of retinal vascular barrier, which can be a target for strategies to establish a curative treatment of DR.
authors.affiliation: Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.|Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Arima
authors.affiliation: Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan.|Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Department of Cell Signaling, Institute of Biomedical Sciences, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D051926:Basigin / Q000037:antagonists & inhibitors / Q000235:genetics*; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000235:genetics; D062507:Claudin-5 / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D051379:Mice; D012160:Retina / Q000187:drug effects / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D013311:Streptozocin / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051242:Caveolin 1; D062507:Claudin-5; C491511:Cldn5 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D051926:Basigin; D013311:Streptozocin