title: Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.
abstract: OBJECTIVE
  Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye.
  
  
  METHODS
  IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.
  
  
  RESULTS
  IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001). Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01), as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001). Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.
  
  
  CONCLUSIONS
  Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Ulbrich
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Schallner
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Loop
authors.affiliation: Eye Center, University Medical Center, Freiburg, Germany.
authors.forename: Wolf Alexander
authors.initials: WA
authors.lastname: Lagrèze
authors.affiliation: Eye Center, University Medical Center, Freiburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Biermann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001128:Argon / Q000008:administration & dosage / Q000627:therapeutic use*; D053148:Caspase 3 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D001128:Argon; D053148:Caspase 3