title: Functional and Structural Evaluation of Sildenafil in a Rat Model of Acute Retinal Ischemia/Reperfusion Injury.
abstract: Retinal ischemia is a common cause of visual impairment and blindness. Sildenafil, a PDE5 inhibitor which inhibits cGMP degradation and in turn prolongs the effect of nitric oxide, has been shown to be protective in a number of ischemia/reperfusion (I/R) injuries, as well as in neuronal damage. We hypothesized that treatment with sildenafil might be neuroprotective in a model of acute retinal I/R injury.
  
  
  
  Anterior chamber cannulation was performed to induce unilateral I/R injury in 38 Lewis rats. Animals received intraperitoneal injections of sildenafil (0.5 and 1 mg/kg once a day, for a period of 7 and 18 days, respectively), or saline. Electroretinography recordings, retinal ganglion cell (RGC) counts following retrograde labeling with fluorogold, histopathology, and immunohistochemistry (IHC) using antibodies against PDE5, NOS2, caspase-3, caspase-9, and Bcl-2 were conducted.
  
  
  
  No significant differences in electroretinography, RGC counts, or retinal morphometry were observed between experimental eyes of sildenafil- and saline-treated animals. A tendency toward less necrosis in histopathology, and a slight trend toward lower PDE5, NOS2, and caspase-9 and higher Bcl-2 IHC scores were evident in experimental retinas of sildenafil-treated animals.
  
  
  
  Electroretinography, RGC counts, and retinal morphometry failed to show any neuroprotective effect of sildenafil in acute retinal I/R injury in rats. A slight positive effect of sildenafil was qualitatively indicated by histopathology and IHC.
authors.affiliation: a Koret School of Veterinary Medicine , The Hebrew University of Jerusalem , Jerusalem , Israel.
authors.forename: Raaya
authors.initials: R
authors.lastname: Ezra-Elia
authors.affiliation: b Ophthalmology Unit, Department of Clinics and Surgery , College of Agronomical and Veterinarian Sciences, University of Estadual Paulista , Jaboticabal , São Paulo , Brazil.
authors.forename: Germana
authors.initials: G
authors.lastname: Alegro da Silva
authors.affiliation: c Veterinary Pathology Service, Department of Veterinary Clinic, Faculty of Veterinary Medicine and Animal Science , University of Estadual Paulista , Botucatu , São Paulo , Brazil.
authors.forename: Diogo Sousa
authors.initials: DS
authors.lastname: Zanoni
authors.affiliation: c Veterinary Pathology Service, Department of Veterinary Clinic, Faculty of Veterinary Medicine and Animal Science , University of Estadual Paulista , Botucatu , São Paulo , Brazil.
authors.forename: Renée
authors.initials: R
authors.lastname: Laufer-Amorim
authors.affiliation: d Department of Veterinary Medicine, Veterinary School , Goias Federal University , Jatai , Goias , Brazil.
authors.forename: Andréia
authors.initials: A
authors.lastname: Vitor Couto do Amaral
authors.affiliation: b Ophthalmology Unit, Department of Clinics and Surgery , College of Agronomical and Veterinarian Sciences, University of Estadual Paulista , Jaboticabal , São Paulo , Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Laus
authors.affiliation: a Koret School of Veterinary Medicine , The Hebrew University of Jerusalem , Jerusalem , Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Ofri
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000150:complications*; D012164:Retinal Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; D053148:Caspase 3; D053453:Caspase 9
keywords: ERG; Electroretinography; I/R; IOP; retinal ganglion cells