title: Protective effect of SUN N8075, a free radical scavenger, against excessive light-induced retinal damage in mice.
abstract: Although dry age-related macular degeneration (AMD) is one of the major causes of blindness, no effective therapies are developed. In this study, we investigated the effects of SUN N8075, a radical scavenger with neuroprotective properties, against light-induced retinal damage used as the model of dry AMD in mice. After dark adaption for 24 h, we exposed the mice at 8000 lx for 3 h. We evaluated the retinal damage by recording the electroretinagram (ERG) and measuring the thickness of outer nuclear layer (ONL) at 5 d after the light exposure. Retinal apoptotic cells were also detected by terminal deoxynucleotidyl transeferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining, and the expression of 8-hydroxy-2-deoxyguanosine (8-OHdG) as an index for oxidative stress at 48 h after exposure to light. In ERG measurement, the intraperitoneal administration of SUN N8075 at 30 mg/kg improved the retinal dysfunction induced by the excess light exposure. In the histological evaluation, SUN N8075 inhibited the reduction of ONL thickness. In addition, SUN N8075 decreased in both numbers of TUNEL- and 8-OHdG-positive cells in ONL. These findings suggest that the systemic administration of SUN N8075 has protective effects on excess light-induced photoreceptor degeneration, via inhibition of oxidative stress.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ojino
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohno
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Otsuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008027:Light; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects*; D010786:Photoreceptor Cells / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D000814:Aniline Compounds; D016166:Free Radical Scavengers; D010879:Piperazines; D017382:Reactive Oxygen Species; C413884:SUN N8075; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine