title: Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension.
abstract: BACKGROUND
  Steroid-induced ocular hypertension is currently treated in the same way as primary open-angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans-resveratrol in rats with steroid-induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans-resveratrol.
  
  
  METHODS
  The oculohypotensive effect of unilateral single-drop application of various concentrations of trans-resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid-induced ocular hypertension. Involvement of AR was studied by observing the alterations of IOP in response to trans-resveratrol after pretreating animals with AR subtype-specific antagonists. Additionally, we used computational methods, including 3D modelling, 3D structure generation and protein-ligand interaction, to determine the AR-trans-resveratrol interaction.
  
  
  RESULTS
  All concentrations of trans-resveratrol produced significant IOP reduction in normotensive rat eyes. Maximum mean IOP reduction of 15.1% was achieved with trans-resveratrol 0.2%. In oculohypertensive rats, trans-resveratrol 0.2% produced peak IOP reduction of 25.2%. Pretreatment with A₁ antagonist abolished the oculohypotensive effect of trans-resveratrol. Pretreatment with A₃ and A₂A AR antagonists produced significant IOP reduction in both treated and control eyes, which was further augmented by trans-resveratrol application in treated eyes. Computational studies showed that trans-resveratrol has highest affinity for A₂B and A₁, followed by A2A and A₃ AR.
  
  
  CONCLUSIONS
  Topically applied trans-resveratrol reduces IOP in rats with steroid-induced ocular hypertension. Trans-resveratrol-induced oculohypotension involves its agonistic activity at the A₁ AR.
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor.
authors.forename: Norhafiza
authors.initials: N
authors.lastname: Razali
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.forename: Puneet
authors.initials: P
authors.lastname: Agarwal
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Minaketan
authors.initials: M
authors.lastname: Tripathy
authors.forename: Sushil
authors.initials: S
authors.lastname: Vasudevan
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Crowston
authors.forename: Nafeeza M
authors.initials: NM
authors.lastname: Ismail
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D003907:Dexamethasone / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009883:Ophthalmic Solutions; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D014065:Tonometry, Ocular
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D013267:Stilbenes; D003907:Dexamethasone; D000077185:Resveratrol
keywords: adenosine receptors; docking simulation; intraocular pressure; resveratrol; topical