title: Ligation of the pterygopalatine and external carotid arteries induces ischemic damage in the murine retina.
abstract: OBJECTIVE
  This study aimed to characterize the functional and morphologic changes in a murine model of ocular ischemic disease caused by vascular occlusion.
  
  
  METHODS
  Retinal ischemia was induced by unilateral ligation of the pterygopalatine artery (PPA) and the external carotid artery (ECA) in anesthetized mice. Changes in ocular blood flow and retinal circulation were evaluated by three different methods: laser speckle blood flow imaging, fundus imaging, and fluorescein isothiocyanate angiography. Five days after reperfusion following 3- or 5-hour ischemia, an electroretinogram (ERG) was recorded, and the retinal histology was examined and quantified. The effects of a free radical scavenger, edaravone, using the model were evaluated by ERG and histologic analysis.
  
  
  RESULTS
  The ligation of both the PPA and the ECA significantly reduced ocular blood flow and narrowed the blood vessels. Five hours of ischemia reduced the a-wave, b-wave, and oscillatory potential amplitudes of the ERG. The number of cells in the ganglion cell layer and the thickness of both the inner plexiform layer and the inner nuclear layer were reduced in the ischemic group. Retinal ischemia caused an increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the inner layer after 21-hour reperfusion following 3-hour ischemia and 19-hour reperfusion following 5-hour ischemia. Edaravone (1 mg/kg, administered intraperitoneally) significantly reduced the retinal ischemic damage.
  
  
  CONCLUSIONS
  These findings indicate that the murine model in which both the PPA and the ECA are ligated may be useful to clarify the pathologic mechanisms of retinal ischemic diseases and to evaluate neuroprotective drugs that target retinal ischemic injury.
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors: Hiromi
authors: H
authors: Ogishima
authors: Shinsuke
authors: S
authors: Nakamura
authors: Tomohiro
authors: T
authors: Nakanishi
authors: Shunsuke
authors: S
authors: Imai
authors: Mamoru
authors: M
authors: Kakino
authors: Fumiya
authors: F
authors: Ishizuka
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity; D002342:Carotid Artery, External / Q000502:physiology*; D002452:Cell Count; D002560:Cerebrovascular Circulation; D003911:Dextrans; D004195:Disease Models, Animal; D000077553:Edaravone; D004596:Electroretinography; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D016166:Free Radical Scavengers / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008297:Male; D051379:Mice; D009880:Ophthalmic Artery / Q000502:physiology*; D056739:Pterygopalatine Fossa / Q000098:blood supply*; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D012164:Retinal Diseases / Q000503:physiopathology* / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000473:pathology
chemical_list: D003911:Dextrans; D016166:Free Radical Scavengers; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D000077553:Edaravone; D000983:Antipyrine