title: Neuroprotective effects of granulocyte colony-stimulating factor on ischemia-reperfusion injury of the retina.
abstract: OBJECTIVE
  It has been reported that granulocyte colony-stimulating factor (G-CSF) provides neuroprotection in models in which neuronal cell death is induced. This research was designed to investigate the effects of G-CSF on neurodegeneration of the inner retinal layer in a rat model of ischemic reperfusion (I/R) injury.
  
  
  METHODS
  Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 45 min in the left eyes of the rats. A sham operation was carried out on the right eyes. G-CSF (100 µg/kg/day in 0.3 ml saline) or the same volume of saline was intraperitoneally injected just before the operation and continued for 4 consecutive days (a total of 5 consecutive days). Morphological examinations, including the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, were performed 7 days after I/R induction. The expression of phosphorylated AKT in the retina was examined by Western blot analysis and immunohistochemistry.
  
  
  RESULTS
  Cell loss in the ganglion cell layer was more significantly reduced in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats (20.3 vs. 6.6%). The inner retinal thickness ratios, such as the inner plexiform layer to the inner limiting membrane/outer nuclear layer and the inner nuclear layer/outer nuclear layer, were significantly better preserved in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats. TUNEL assays showed fewer apoptotic cells in the retinal sections of the I/R-induced eyes of the G-CSF-injected rats. The phosphorylation of AKT (p-AKT/AKT) was upregulated in the retinas of the I/R-induced eyes of the G-CSF-injected rats.
  
  
  CONCLUSIONS
  Our results demonstrated that systemic injection of G-CSF can protect retinal ganglion cells and inner retinal layers from I/R injury. The effects could be associated with the activation of AKT.
authors.affiliation: Department of Ophthalmology, Kansai Medical University, Moriguchi City, Osaka, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Shima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Keizo
authors.initials: K
authors.lastname: Minamino
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Seiji
authors.initials: S
authors.lastname: Yanai
authors.forename: Kanji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt