Abstract
Purpose: :
Mice are now widely used in glaucoma research yet the physiology of murine aqueous humour drainage is incompletely understood. Here we determine the relationship between intraocular pressure (IOP) and aqueous outflow resistance, and measure ocular compliance and washout rate.
Methods: :
Eyes from adult mice of either sex (C57BL/6 background) were enucleated, cannulated with a 33G Nanofil needle (WPI), and attached to a perfusion system consisting of a pressure transducer and a computer-controlled syringe pump that delivered a variable flow rate to the anterior chamber to maintain a desired IOP. Eyes were perfused with phosphate buffered saline following one of two regimens: 1) at 8 mmHg constant pressure for 2-3 hours, corresponding to ~15 mmHg in vivo; 2) at constant pressures of 8, 15 and 4 mmHg for 20 min each, with stepwise changes between each pressure level. Washout rate was estimated according to Erickson-Lamy et al. (IOVS,1990). Needle resistance, perfusion system compliance and ocular compliance were also measured.
Results: :
At 8 mmHg, eyes had a stable baseline outflow resistance of 59.1 ± 9.9 mmHg min/uL (facility = 0.017 ± 0.003 uL/min/mmHg; mean ± SD, n = 22). Outflow resistance was 35 ± 6 and 81 ± 24 mmHg/uL/min at 4 mmHg and 15 mmHg respectively, increasing with IOP (p<0.005, linear regression, r2=0.97). At 8 mmHg, washout was not observed (insignificant facility decrease of 0.4 ± 8 % of starting facility per hour; n=7). Initial studies revealed that outflow resistance measurements were sensitive to the compliance of the perfusion system, and even when using high pressure tubing, the system compliance (0.10 uL/mmHg) was comparable to the ocular compliance (0.078 ± 0.007 uL/mmHg; n = 4). In contrast, the resistance of the perfusion system was negligible (0.77 ± 0.05 mmHg min/uL) compared with the eye.
Conclusions: :
Similar to human eyes, mouse eyes show a pressure-dependent outflow facility and no detectable washout. Mouse seems to be the only species (other than human) where washout is absent. Our measured outflow facility is ~3-fold greater than previous in vivo reports (Aihara et al, IOVS, 2003, Crowston et al, IOVS, 2004 and Zhang et al, JGP, 2002), which may be due to differences in measurement techniques or mouse strain.
Keywords: anterior chamber • intraocular pressure • aqueous