title: Edaravone, an ROS scavenger, ameliorates photoreceptor cell death after experimental retinal detachment.
abstract: OBJECTIVE
  To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD).
  
  
  METHODS
  RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively.
  
  
  RESULTS
  RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration.
  
  
  CONCLUSIONS
  Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage.
authors.affiliation: Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Mi In
authors.initials: MI
authors.lastname: Roh
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Aristomenis
authors.initials: A
authors.lastname: Thanos
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D018384:Oxidative Stress / Q000187:drug effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050050:Protein Carbonylation; D051381:Rats; D011914:Rats, Inbred BN; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012163:Retinal Detachment / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000447:Aldehydes; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D020169:Caspases; C027576:4-hydroxy-2-nonenal; D000077553:Edaravone; D000983:Antipyrine