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Alexandra Boussommier Calleja, Yuan Lei, W. Dan Stamer, C. Ross Ethier, Darryl R. Overby; Sphingosine 1-phosphate Decreases Conventional Outflow Facility In The Mouse Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4631.
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© ARVO (1962-2015); The Authors (2016-present)
Sphingosine 1-phosphate (S1P) is a bioactive lipid that rapidly reduces outflow facility in porcine and human eyes, likely through its effects on endothelial permeability and cellular contractility. To determine whether the pharmacology of murine outflow mimics that of human, we tested the effects of S1P on conventional facility and unconventional outflow in enucleated mouse eyes.
Ten eyes from C57BL/6 mice were enucleated and perfused ex vivo at multiple perfusion pressures (4, 8, 15 and 25 mmHg) using a computer-controlled perfusion system optimised for the mouse eye. Experimental eyes (N=6) were perfused with 5 µM S1P in Dulbecco’s PBS + 5.5 mM glucose + 0.2% bovine serum albumin, while control eyes (N=4) received the same perfusion fluid without S1P. Pooled data were fit to the Goldmann equation to calculate conventional outflow facility (C; corresponding to the slope) and the unconventional flow rate (Fu; corresponding to the intercept) from the flow-pressure relationship
Perfusion data were well described by the Goldmann equation, exhibiting a linear flow-vs-pressure relationship between 4 and 25 mmHg with a non-zero flow intercept when extrapolated to 0 mmHg. At 8, 15 and 25 mmHg, S1P significantly reduced flow rate (p < 0.02). The slope of the flow-vs-pressure relationship was 0.0095±0.0014 vs. 0.0045±0.0011 µL/min/mmHg (mean±SEM; p=0.03) in control vs. experimental eyes, corresponding to a 52.6% decrease in C in response to S1P. In contrast, the intercept of the flow-vs-pressure relationship representing Fu was unchanged (0.0323±0.0134 vs. 0.0236±0.004 µL/min ;p = 0.57) between control and experimental eyes.
S1P rapidly and robustly decreases conventional outflow facility in the mouse eye, without appearing to affect unconventional (pressure-independent) outflow, similar to the response observed in human eyes. This enhances confidence in the mouse eyes as a model for trabecular outflow in human eyes.
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