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Michael Madekurozwa, Andrew Feola, C Ross Ethier, Darryl R Overby, Joseph Sherwood; Comparison of Pressure-Dependent Facility in Rodent Eyes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1060.
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© ARVO (1962-2015); The Authors (2016-present)
Mice are commonly used to study aqueous humor dynamics, due to similarities with humans in their ocular anatomy, physiology and pharmacology. However, outflow facility in humans decreases with increasing pressure, which is attributed to pressure-induced collapse of Schlemm’s canal , whereas the opposite is true in mice . We compared the pressure-dependence of outflow facility between rat and mouse eyes using ex vivo perfusions to examine which species better matched the response observed in humans.
Enucleated eyes from 8 Brown Norway rats (3-4 months) and 66 C57BL/6 mice (2-3 months) were perfused via the anterior chamber through a 33G needle. A multistep perfusion was carried out using iPerfusion, which utilizes a Sensirion flow sensor and an automated pressure reservoir. Having confirmed that both species exhibit zero flow at zero pressure, the model Q=Cr(P/Pr)βP was fit to the data , where Cr is the facility at reference pressure Pr, and β is a parameter characterizing the pressure-dependent change in facility, with a negative β corresponding to decreasing facility with increasing pressure. Note β=-0.25±0.03 for humans (derived by fitting data from ). Unpaired t-tests were used to evaluate whether β differed significantly from human values. Data are reported as mean ± 95% margin of error.
For rats, the Q-P response curves downwards (Fig. 1a), i.e. facility decreases with increasing pressure. The situation is opposite in mice (Fig. 1b).For mice, β=0.75±0.09 (Fig. 1c), which is significantly different from humans (p<10-12, n=66). For rats, β=-0.36±0.20, which is not significantly different from the value for humans (p=0.24, n=8), but is significantly different from zero (p=0.004).
The Q-P response in rats mimics that observed in humans, where facility decreases with increasing pressure, while mouse eyes exhibit the opposite. Understanding the anatomical basis for these differences may provide insight into trabecular meshwork biomechanics that regulate outflow. As the shape of the Q-P relationship is associated with SC collapse , rats may have advantages over mice for studies of TM/SC biomechanics as occurs in humans. Brubaker 1975 IOVS 14:286-292.  Sherwood et al. 2016 PLoS One 11(3):e0150694.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Figure 1. Sample Q-P plots for (a) rat and (b) mouse eyes. (c) Cello plot of β (described in ). Dashed line indicates β for humans.
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