title: Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs.
abstract: Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia; Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, 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; Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Faculty 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: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia; Faculty of Medicine, Drug Discovery and Health Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, 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; Faculty of Medicine, Drug Discovery and Health Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Methil
authors.initials: M
authors.lastname: Kannan 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; Faculty of Medicine, Drug Discovery and Health Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Nor
authors.initials: N
authors.lastname: Salmah Bakar
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia; Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Nafeeza M
authors.initials: NM
authors.lastname: Ismail
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D002374:Catalase / Q000378:metabolism; D003907:Dexamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; D013449:Sulfonamides; D013876:Thiophenes; D010862:Pilocarpine; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D003907:Dexamethasone; D013999:Timolol; C062765:dorzolamide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Histology; IOP; Rats; Retina; Steroid; Trabecular meshwork