title: Statin inhibits leukocyte-endothelial interaction and prevents neuronal death induced by ischemia-reperfusion injury in the rat retina.
abstract: BACKGROUND
  Retinal ishchemia-induced neuronal death is believed to be a direct causal process in the development of many ocular diseases. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, statin, is known to improve endothelial function in proinflammatory conditions.
  
  
  OBJECTIVE
  To investigate the effects of statin on leukocyte accumulation during ischemia-reperfusion injury and on subsequent retinal damage.
  
  
  METHODS
  Transient retinal ischemia was induced in Long-Evans rats for 60 minutes using temporal ligation of the optic nerve. Leukocyte-endothelial interactions in the postischemic retina were evaluated in vivo with a scanning laser ophthalmoscope. Statin was administered 5 minutes before the induction of retinal ischemia. P-selectin and intercellular adhesion molecule-1 (ICAM-1) gene expression in the postischemic retina were studied with the semiquantitative polymerase chain reaction. Histologic studies were carried out to evaluate retinal damage.
  
  
  RESULTS
  The preadministration of statin attenuated the rolling and accumulation of leukocytes, decreased P-selectin and ICAM-1 expression, and reduced the number of apoptotic cells in the retina. Furthermore, histologic evaluation 168 hours after reperfusion showed that statin significantly diminished the resultant retinal tissue damage. The neuroprotective effect of statin was abolished when it was administered along with a nitric oxide synthase inhibitor, nitroglycerine-nitro-L-arginine methyl ester.
  
  
  CONCLUSIONS
  Statin may exert neuroprotective effects by inhibiting leukocyte-endothelial interaction through the release of nitric oxide from the endothelium.
  
  
  CONCLUSIONS
  As a result of its efficacy in preventing retinal neuronal death, statin may be developed into a novel therapeutic modality for many ocular ischemic diseases.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. megumi@kuhp.kyoto-u.ac.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Honjo
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nishijima
authors.forename: Junichi
authors.initials: J
authors.lastname: Kiryu
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Honda
authors.forename: Beatrice Y J T
authors.initials: BY
authors.lastname: Yue
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
mesh_terms: D000165:Acridine Orange; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D005456:Fluorescent Dyes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017035:Pravastatin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012171:Retinal Vessels / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D019007:P-Selectin; D011725:Pyridines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C086276:cerivastatin; D000165:Acridine Orange; D017035:Pravastatin