NDLI: Pharmacologic Manipulation of Conventional Outflow Facility in Ex Vivo Mouse Eyes

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Pharmacologic Manipulation of Conventional Outflow Facility in Ex Vivo Mouse Eyes

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Pharmacologic Manipulation of Conventional Outflow Facility in Ex Vivo Mouse Eyes

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Boussommier-Calleja, Alexandra Stamer, W. Daniel Woodward, David F. Ethier, C. Ross Bertrand, Jacques Overby, Darryl R.
Description	Country affiliation: United kingdom Author Affiliation: Boussommier-Calleja A ( Department of Bioengineering, Imperial College London, London, UK.)
Abstract	PURPOSE: Mouse models are useful for glaucoma research, but it is unclear whether intraocular pressure (IOP) regulation in mice operates through mechanisms similar to those in humans. Our goal was to determine whether pharmacologic compounds that affect conventional outflow facility in human eyes exert similar effects in C57BL/6 mice. METHODS: A computerized perfusion system was used to measure conventional outflow facility in enucleated mouse eyes ex vivo. Paired eyes were perfused sequentially, either immediately after enucleation or after 3 hours storage at 4°C. Three groups of experiments examined sphingosine 1-phosphate (S1P), S1P with antagonists to S1P(1) and S1P(2) receptors, and the prostanoid EP(4) receptor agonist 3,7-dithia PGE(1). We also examined whether a 24-hour postmortem delay affected the response to 3,7-dithia prostaglandin E(1) (PGE(1)). RESULTS: S1P decreased facility by 39%, and was blocked almost completely by an S1P(2), but not S1P(1), receptor antagonist. The S1P(2) receptor antagonist alone increased facility nearly 2-fold. 3,7-dithia PGE(1) increased facility by 106% within 3 hours postmortem. By 24 hours postmortem, the facility increase caused by 3,7-dithia PGE(1) was reduced 3-fold, yet remained statistically detectable. CONCLUSIONS: C57BL/6 mice showed opposing effects of S1P(2) and EP(4) receptor activation on conventional outflow facility, as observed in human eyes. Pharmacologic effects on facility were detectable up to 24 hours postmortem in enucleated mouse eyes. Mice are suitable models to examine the pharmacology of S1P and EP(4) receptor stimulation on IOP regulation as occurs within the conventional outflow pathway of human eyes, and are promising for studying other aspects of aqueous outflow dynamics.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.12-9923
Journal	Investigative Opthalmology & Visual Science
Issue Number	9
Volume Number	53
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2012-08-24
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Alprostadil Analogs & Derivatives Aqueous Humor Metabolism Disease Models, Animal Lysophospholipids Pharmacology Sphingosine Trabecular Meshwork Drug Effects Animals Eye Enucleation Intraocular Pressure Physiology Mice Mice, Inbred C57bl Organ Preservation Receptors, Lysosphingolipid Antagonists & Inhibitors Receptors, Prostaglandin E, Ep4 Subtype Agonists Tonometry, Ocular 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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