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Thirty\u2010six rats were divided into a control group (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>6) and two experimentally induced ischaemia\u2013reperfusion groups (7 and 21\u00a0days; <jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>15 per group). The induced ischaemia\u2013reperfusion groups were treated with sildenafil for 7 and 21\u00a0days (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>10 per group), and 10 animals were treated with a placebo for the same period (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>5 per group). Paracentesis of the anterior chamber was performed with a 30\u2010G needle attached to a saline solution (0.9%) bag positioned at a height of 150\u00a0cm above the eye for 60\u00a0min. Intraocular pressure was measured by rebound tonometer (TonoVet<jats:sup>\u00ae<\/jats:sup>). The eyes were analysed by histology and morphometry, and by immunohistochemistry and <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> for expression of <jats:italic>Caspase\u20107<\/jats:italic>,<jats:italic> Caspase\u20106<\/jats:italic>,<jats:italic> Caspase\u20109<\/jats:italic>,<jats:italic> Tnf\u2010r2<\/jats:italic>,<jats:italic> Fas\u2010l<\/jats:italic>,<jats:italic> Bcl\u20102<\/jats:italic> and <jats:italic>Bax<\/jats:italic>. Sildenafil\u2010treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo\u2010treated counterparts at both 7 and 21\u00a0days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (<jats:styled-content style=\"fixed-case\">SG<\/jats:styled-content>), with a cell count closer to control than in the placebo groups (<jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>). Caspase\u20107 expression was significantly higher in both treated groups at 7\u00a0days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in <jats:styled-content style=\"fixed-case\">SG <\/jats:styled-content><jats:italic>Bax<\/jats:italic> and <jats:italic>Caspase\u20106<\/jats:italic> expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro\u2010apoptotic factors and decrease in the anti\u2010apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in <jats:styled-content style=\"fixed-case\">SG<\/jats:styled-content> similar to the controls.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iep.12233","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T09:51:36Z","timestamp":1504173096000},"page":"147-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia\u2013reperfusion injury model treated with sildenafil citrate"],"prefix":"10.1111","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-1585","authenticated-orcid":false,"given":"Diogo S.","family":"Zanoni","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinic School of Veterinary Medicine and Animal Science University Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germana A.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic and Surgery School of Veterinary Medicine and Animal Science University Estadual Paulista Jaboticabal SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raaya","family":"Ezra\u2010Elia","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine The Hebrew University of Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcio","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic School of Veterinary Medicine and Animal Science University Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliany G.","family":"Quitzan","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anesthesiology School of Veterinary Medicine and Animal Science University Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron","family":"Ofri","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine The Hebrew University of Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 L.","family":"Laus","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic and Surgery School of Veterinary Medicine and Animal Science University Estadual Paulista Jaboticabal SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renee","family":"Laufer\u2010Amorim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic School of Veterinary Medicine and Animal Science University Estadual Paulista Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2011.11.002"},{"key":"e_1_2_8_3_1","first-page":"880","article-title":"Estimation of prevalence and incidence rates and causes of blindness in Israel, 1998\u20102003","volume":"8","author":"Avisar R.","year":"2006","journal-title":"Isr. 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