title: Lutein acts via multiple antioxidant pathways in the photo-stressed retina.
abstract: Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein's effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes.
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.|Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kamoshita
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Toda
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Osada
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.|Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Narimatsu
authors.affiliation: Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.|Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008027:Light; D014975:Lutein / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D014975:Lutein; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2