title: Protective effect of pioglitazone on retinal ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  To investigate the protective effect of pioglitazone on the rat retina after ischemia/reperfusion (I/R) injury and to explore its possible mechanisms.
  
  
  METHODS
  Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 60 minutes, and pioglitazone was delivered 3 hours before the I/R. Retinal damage was quantified by measuring the thickness of the retina, the functional changes of visual evoked potential (VEP) and electroretinography (ERG), and the number of retinal ganglion cells (RGCs) at 7 days after I/R injury. Real-time PCR and Western blot analysis were performed to measure the glial fibrillary acidic protein (GFAP) expression. Retinal cell apoptosis was detected by TUNEL assay at 24 hours after reperfusion. Nuclear factor-κB (NF-κB), Bax, and Bcl-2 in the retina were determined by Western blot analysis.
  
  
  RESULTS
  The I/R produced a degenerative effect primarily in the ganglion cell layer, inner plexiform layer, and inner nuclear layer. Pioglitazone maintained the retinal thickness, promoted the survival of RGCs, and attenuated the destruction of ERG and VEP caused by I/R. Pioglitazone pretreatment also suppressed NF-κB activation and altered GFAP overexpression. The number of TUNEL-labeled cells significantly decreased in the retinas pretreated with pioglitazone, and the Bax-Bcl-2 ratio was much lower in the retinas pretreated with pioglitazone than in the I/R group.
  
  
  CONCLUSIONS
  Pioglitazone could inhibit activation of the glia cells, prevent cell apoptosis, and protect the retina from subsequent cellular damage caused by the retinal I/R. The possible mechanism might involve the NF-κB pathway.
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhang
authors.forename: Yi-Qin
authors.initials: YQ
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Ye
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000166:cytology; D012171:Retinal Vessels / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D005904:Glial Fibrillary Acidic Protein; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; D000077205:Pioglitazone
keywords: NF-κB; PPAR-γ; glia activation; pioglitazone; retinal ischemia/reperfusion