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Alexandra Boussommier-Calleja, Jacques Bertrand, David F. Woodward, C. Ross Ethier, W. Daniel Stamer, Darryl R. Overby; Pharmacologic Manipulation of Conventional Outflow Facility in Ex Vivo Mouse Eyes. Invest. Ophthalmol. Vis. Sci. 2012;53(9):5838-5845. doi: 10.1167/iovs.12-9923.
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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.
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 S1P1 and S1P2 receptors, and the prostanoid EP4 receptor agonist 3,7-dithia PGE1. We also examined whether a 24-hour postmortem delay affected the response to 3,7-dithia prostaglandin E1 (PGE1).
S1P decreased facility by 39%, and was blocked almost completely by an S1P2, but not S1P1, receptor antagonist. The S1P2 receptor antagonist alone increased facility nearly 2-fold. 3,7-dithia PGE1 increased facility by 106% within 3 hours postmortem. By 24 hours postmortem, the facility increase caused by 3,7-dithia PGE1 was reduced 3-fold, yet remained statistically detectable.
C57BL/6 mice showed opposing effects of S1P2 and EP4 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 EP4 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.
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