title: Topical trans-resveratrol ameliorates steroid-induced anterior and posterior segment changes in rats.
abstract: Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia. Electronic address: norhafiza8409@salam.uitm.edu.my.
authors.forename: Norhafiza
authors.initials: N
authors.lastname: Razali
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: School of Medicine, International Medical University, IMU Clinical School, Department of Ophthalmology, Jalan Rasah, Seremban, Malaysia.
authors.forename: Puneet
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Universiti Teknologi MARA, Faculty of Pharmacy, Dept. of Pharmaceutics, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Minaketan
authors.initials: M
authors.lastname: Tripathy
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Marina Y
authors.initials: MY
authors.lastname: Kapitonova
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Methil K
authors.initials: MK
authors.lastname: Kutty
authors.affiliation: Pathological Anatomy Department, Volgograd State Medical University, 1, Pavshikh Bortsov Square, Volgograd, 400131, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Smirnov
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Zalizah
authors.initials: Z
authors.lastname: Khalid
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Nafeeza M
authors.initials: NM
authors.lastname: Ismail
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001082:Aqueous Humor / Q000201:enzymology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009883:Ophthalmic Solutions; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage*; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000473:pathology*
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D013267:Stilbenes; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D000077185:Resveratrol
keywords: Glaucoma; Intraocular pressure; Resveratrol; Retina; Steroid-induced; Trabecular meshwork