title: Heme oxygenase-1 induced in muller cells plays a protective role in retinal ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  To investigate the protective roles played by heme oxygenase (HO)-1 and -2 in the rat retina after ischemia-reperfusion injury.
  
  
  METHODS
  Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mmHg for 60 minutes. The expression of HO-1 and -2 in the retina was determined by Western blot, real-time polymerase chain reaction (PCR), and immunohistochemistry. To inhibit the upregulation of HO-1, short interfering (si)RNA of HO-1 was injected intravitreally before ischemia and that of green fluorescent protein (GFP) was used as the control. Muller cell damage was assessed by counting the number of S-100-positive cells. The number of macrophages invading the retina was determined by counting the number of ED-1-positive cells.
  
  
  RESULTS
  The expression of HO-1 mRNA and protein was upregulated at 6 hours after reperfusion and peaked at 12 to 24 hours, whereas that of HO-2 was not altered. HO-1 immunoreactivities were detected in Muller cells at 24 hours after reperfusion, and HO-2 immunoreactivities were detected in retinal cells. The HO-1 expression in the retina treated with siRNA of HO-1 was reduced at 12 and 24 hours after reperfusion compared with that injected with siRNA of GFP. The number of S-100-positive cells at 24 hours after reperfusion decreased significantly in retinas treated with HO-1 siRNA (P <0.01). The number of macrophages that had infiltrated the retina was increased in retinas pretreated with the siRNA of HO-1 compared with those treated with siRNA of GFP. On day 14 after reperfusion, HO-1 siRNA-treated retinas showed severe retinal injury and destruction of the retinal architecture.
  
  
  CONCLUSIONS
  HO-1 promotes the survival of Muller cells after ischemia-reperfusion injury. Because inhibition of the upregulation of HO-1 resulted in an infiltration of inflammatory cells and destruction of the retina, the authors conclude that HO-1 induced in Muller cells plays a protective role in retinal ischemia-reperfusion.
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Arai-Gaun
authors.forename: Naomichi
authors.initials: N
authors.lastname: Katai
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ohta
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D053331:Ectodysplasins; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009457:Neuroglia / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000201:enzymology / Q000517:prevention & control*; D009418:S100 Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053331:Ectodysplasins; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D009418:S100 Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2