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However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans\u2010resveratrol in rats with steroid\u2010induced ocular hypertension and involvement of adenosine receptors (<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>) in intraocular pressure (<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>) lowering effect of trans\u2010resveratrol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The oculohypotensive effect of unilateral single\u2010drop application of various concentrations of trans\u2010resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid\u2010induced ocular hypertension. Involvement of<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>was studied by observing the alterations of<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>in response to trans\u2010resveratrol after pretreating animals with<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>subtype\u2010specific antagonists. Additionally, we used computational methods, including 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>modelling, 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>structure generation and protein\u2013ligand interaction, to determine the<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>\u2013trans\u2010resveratrol interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All concentrations of trans\u2010resveratrol produced significant<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>reduction in normotensive rat eyes. Maximum mean<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>reduction of 15.1% was achieved with trans\u2010resveratrol 0.2%. In oculohypertensive rats, trans\u2010resveratrol 0.2% produced peak<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>reduction of 25.2%. Pretreatment with<jats:styled-content style=\"fixed-case\">A<jats:sub>1<\/jats:sub><\/jats:styled-content>antagonist abolished the oculohypotensive effect of trans\u2010resveratrol. Pretreatment with<jats:styled-content style=\"fixed-case\">A<jats:sub>3<\/jats:sub><\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">A<jats:sub>2A<\/jats:sub>AR<\/jats:styled-content>antagonists produced significant<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>reduction in both treated and control eyes, which was further augmented by trans\u2010resveratrol application in treated eyes. Computational studies showed that trans\u2010resveratrol has highest affinity for<jats:styled-content style=\"fixed-case\">A<jats:sub>2B<\/jats:sub><\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">A<jats:sub>1<\/jats:sub><\/jats:styled-content>, followed by<jats:styled-content style=\"fixed-case\">A<jats:sub>2A<\/jats:sub><\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">A<jats:sub>3<\/jats:sub>AR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Topically applied trans\u2010resveratrol reduces<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>in rats with steroid\u2010induced ocular hypertension. Trans\u2010resveratrol\u2010induced oculohypotension involves its agonistic activity at the<jats:styled-content style=\"fixed-case\">A<jats:sub>1<\/jats:sub>AR<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12375","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T04:11:14Z","timestamp":1404447074000},"page":"54-66","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Role of adenosine receptors in resveratrol\u2010induced intraocular pressure lowering in rats with steroid\u2010induced ocular hypertension"],"prefix":"10.1111","volume":"43","author":[{"given":"Norhafiza","family":"Razali","sequence":"first","affiliation":[{"name":"Faculty of Medicine Brain and Neuroscience Communities of Research Universiti Teknologi MARA (UiTM) Shah Alam 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