title: Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation.
abstract: Light damage to the retina accelerates retinal degeneration in human diseases and rodent models. Recently, the polyphenolic phytoalexin resveratrol has been shown to exert various bioactivities in addition to its classical antioxidant property. In the present study, we investigated the effect of resveratrol on light-induced retinal degeneration together with its underlying molecular mechanisms. BALB/c mice with light exposure (5000-lux white light for 3 hours) were orally pretreated with resveratrol at a dose of 50 mg/kg for 5 days. Retinal damage was evaluated by TdT-mediated dUTP nick-end labeling, outer nuclear layer morphometry, and electroretinography. Administration of resveratrol to mice with light exposure led to a significant suppression of light-induced pathological parameters, including TdT-mediated dUTP nick-end labeling-positive retinal cells, outer nuclear layer thinning, and electroretinography changes. To clarify the underlying molecular mechanisms, the nuclear translocation of activator protein-1 subunit c-fos was evaluated by enzyme-linked immunosorbent assay, and the retinal activity of sirtuin 1 was measured by deacetylase fluorometric assay. Retinal activator protein-1 activation, up-regulated following light exposure, was significantly reduced by application of resveratrol. In parallel, retinal sirtuin 1 activity, reduced in animals with light damage, was significantly augmented by resveratrol treatment. Our data suggest the potential use of resveratrol as a therapeutic agent to prevent retinal degeneration related to light damage.
authors: Laboratories of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan.
authors: Shunsuke
authors: S
authors: Kubota
authors: Toshihide
authors: T
authors: Kurihara
authors: Mari
authors: M
authors: Ebinuma
authors: Miyuki
authors: M
authors: Kubota
authors: Kenya
authors: K
authors: Yuki
authors: Mariko
authors: M
authors: Sasaki
authors: Kousuke
authors: K
authors: Noda
authors: Yoko
authors: Y
authors: Ozawa
authors: Yuichi
authors: Y
authors: Oike
authors: Susumu
authors: S
authors: Ishida
authors: Kazuo
authors: K
authors: Tsubota
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000077185:Resveratrol; D012160:Retina / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D018808:Transcription Factor AP-1; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol