title: Edaravone is a free radical scavenger that protects against laser-induced choroidal neovascularization in mice and common marmosets.
abstract: Choroidal neovascularization (CNV) is a main characteristic in exudative type of age-related macular degeneration (AMD). Our study aimed to evaluate the effects of edaravone, a free radical scavenger on laser-induced CNV. CNV was induced by laser photocoagulation to the subretinal choroidal area of mice and common marmosets. Edaravone was administered either intraperitoneally twice a day for 2 weeks or intravenously just once after laser photocoagulation. The effects of edaravone on laser-induced CNV were evaluated by fundus fluorescein angiography, CNV area measurements, and the expression of 4-hydroxy-2-nonenal (4-HNE) modified proteins, a marker of oxidative stress. Furthermore, the effects of edaravone on the production of H2O2-induced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF)-induced cell proliferation were evaluated using human retinal pigment epithelium cells (ARPE-19) and human retinal microvascular endothelial cells, respectively. CNV areas in the edaravone-treated group were significantly smaller in mice and common marmosets. The expression of 4-HNE modified proteins was upregulated 3 h after laser photocoagulation, and intravenously administered edaravone decreased it. In in vitro studies, edaravone inhibited H2O2-induced ROS production and VEGF-induced cell proliferation. These findings suggest that edaravone may protect against laser-induced CNV by inhibiting oxidative stress and endothelial cell proliferation.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: shimazawa@gifu-pu.ac.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Takata
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002144:Callithrix; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007834:Lasers / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D000077553:Edaravone; D000983:Antipyrine
keywords: 4-hydroxy-2-nonenal; Common marmosets; Edaravone; Free radical scavenger; Human retinal microvascular endothelial cells; Human retinal pigment epithelium cells; Laser-induced choroidal neovascularization model; Reactive oxygen species