NDLI: Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator.

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Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator.

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Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kumar, Sandeep Danias, John Gerometta, Rosana Alvarez, Larry Shah, Shaily Candia, Oscar
Description	Country affiliation: Argentina Author Affiliation: Gerometta R ( Departamento de Oftalmología, UNNE, Corrientes, Argentina.)
Abstract	PURPOSE: To investigate whether tissue plasminogen activator (tPA) can prevent and/or reverse steroid-induced IOP elevation in an ovine model. METHODS: Three animal groups were subjected to bilateral steroid-induced IOP elevation using thrice daily topical ocular prednisolone administration. In the first group (N = 8), one eye each of two sheep was injected intravitreally with 100 µg, 200 µg, 500 µg, or 1 mg human recombinant tPA, while contralateral eyes received vehicle. In the second group (N = 2), one eye was injected intravitreally with tPA (100 µg), while contralateral eyes received vehicle containing L-arginine. In the third group (N = 4), each animal received intravitreal tPA in one eye concurrently with initiation of bilateral steroid administration. IOP was monitored for the duration of the experiment. Tissues from eyes of the third group were used to determine relative gene expression. RESULTS: In the first and second groups, IOP decreased by 9.7 (±2.8) and 9.7 (±1.6) mm Hg, respectively, 24 hours after tPA administration. In the third group, tPA-treated eyes did not develop IOP elevation with ΔIOP of 11.8 (±1.3) mm Hg 8 days later. In all tPA-treated eyes, IOP remained low until the end of the study. mRNA levels in the trabecular meshwork were decreased for plasminogen activator tissue (PLAT), increased for matrix-metalloproteinase 1 (MMP-1), and stable for plasminogen activator inhibitor 1 (PAI-1), MMP-2, MMP-9, and MMP-13 in tPA-treated eyes compared with contralateral controls. PAI-1 mRNA levels in ciliary processes also remained similar. CONCLUSIONS: Recombinant human tPA is effective in both preventing and reversing steroid-induced IOP elevation in sheep. Tissue plasminogen activator may be useful as a therapeutic agent in steroid-induced glaucoma.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.13-12801
Journal	Investigative Opthalmology & Visual Science
Issue Number	13
Volume Number	54
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2013-12-03
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Intraocular Pressure Drug Effects Ocular Hypertension Drug Therapy Tissue Plasminogen Activator Administration & Dosage Animals Disease Models, Animal Disease Progression Dose-response Relationship, Drug Fibrinolytic Agents Gene Expression Regulation Intravitreal Injections Matrix Metalloproteinases Biosynthesis Genetics Chemically Induced Physiopathology Prednisolone Toxicity Real-time Polymerase Chain Reaction Trabecular Meshwork Enzymology Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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