Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension

• Published in: Clinical and Experimental Ophthalmology
• Main Author: Razali N.; Agarwal R.; Agarwal P.; Kumar S.; Tripathy M.; Vasudevan S.; Crowston J.G.; Ismail N.M.
• Format: Article
• Language: English
• Published: Blackwell Publishing 2015
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84921441380&doi=10.1111%2fceo.12375&partnerID=40&md5=3822fbe3a9012aa55017fb6b5cc4c69d

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. Conclusion: 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. © 2014 Royal Australian and New Zealand College of Ophthalmologists.