title: Inhalative preconditioning with hydrogen sulfide attenuated apoptosis after retinal ischemia/reperfusion injury.
abstract: OBJECTIVE
  Retinal ischemia/reperfusion (I/R) injury plays an important role in the pathophysiology of various ocular diseases. Retinal ganglion cells (RGCs) are particularly vulnerable to ischemia. Hydrogen sulfide (H(2)S) was recently shown to be neuroprotective in the brain and retina due to its antiapoptotic effects. Rapid preconditioning of retinal neurons by inhaled H(2)S before I/R injury may reduce apoptosis in the rat retina.
  
  
  METHODS
  I/R injury was created on the left eye of rats (n=8) with or without inhaled H(2)S preconditioning (80 ppm) for one hour before ischemia. Densities of fluorogold prelabeled RGCs were analyzed 7 days after injury in retinal whole mounts. Retinal tissue was harvested to analyze protein expression of heat shock protein (HSP)-90 and the mitogen-activated protein kinases (MAPKs) c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38 to elucidate a possible pathway of neuroprotection. DNA binding activity of the transcription factors nuclear factor-kappa-light-chain-enhancer of activated B-cells (NF-κB), cyclic adenosine monophosphate response element binding protein (CREB), and heat shock element (HSE), as well as caspase-3 cleavage and activity, were determined. Retinal sections were further assessed using anti-glial fibrillary acidic protein staining.
  
  
  RESULTS
  RGC death after I/R injury decreased by 41.5% after H(2)S preconditioning compared to room air (p<0.001). H(2)S inhalation before ischemia reduced caspase-3 cleavage (p<0.001) and attenuated caspase-3 activity (p<0.001). Furthermore, HSP-90 expression was significantly elevated in the retina after H(2)S preconditioning. NF-κB but not CREB or HSE showed specific, H2S-dependent regulation, as well as the MAPKs ERK1/2 and JNK but not p38.
  
  
  CONCLUSIONS
  H(2)S preconditioning mediates antiapoptotic effects in retinal I/R injury, thus exhibiting neuroprotection. Based on these observations, H(2)S could represent a novel and promising therapeutic agent to counteract neuronal injuries in the eye. Further studies are needed to prove H(2)S's neuroprotective propensity using a postconditioning approach.
authors.affiliation: University Eye Hospital Freiburg, Freiburg, Germany. julia.biermann@uniklinik-freiburg.de
authors.forename: Julia
authors.initials: J
authors.lastname: Biermann
authors.forename: Wolf A
authors.initials: WA
authors.lastname: Lagrèze
authors.forename: Nils
authors.initials: N
authors.lastname: Schallner
authors.forename: Christian I
authors.initials: CI
authors.lastname: Schwer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D061945:Caspase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018841:HSP90 Heat-Shock Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide