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Role of adenosine receptors in resveratrol‐induced intraocular pressure lowering in rats with steroid‐induced ocular hypertension
Author(s) -
Razali Norhafiza,
Agarwal Renu,
Agarwal Puneet,
Kumar Sunil,
Tripathy Minaketan,
Vasudevan Sushil,
Crowston Jonathan G,
Ismail Nafeeza M
Publication year - 2014
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.12375
Subject(s) - resveratrol , ocular hypertension , intraocular pressure , medicine , glaucoma , pharmacology , antagonist , receptor , adenosine , endocrinology , ophthalmology
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 3 D modelling, 3 D 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 A 1 antagonist abolished the oculohypotensive effect of trans‐resveratrol. Pretreatment with A 3 and A 2A 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 A 2B and A 1 , followed by A 2A and A 3 AR . Conclusion Topically applied trans‐resveratrol reduces IOP in rats with steroid‐induced ocular hypertension. Trans‐resveratrol‐induced oculohypotension involves its agonistic activity at the A 1 AR .