Purchase this article with an account.
Darryl R Overby, Michael Madekurozwa, W Daniel Stamer, Joseph Sherwood; Modulation of outflow facility by the ocular pulse. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3971.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
IOP is not static, but rather oscillates by 2-3 mmHg due to cardiac pulsations in ocular blood volume known as the ocular pulse. Fluid mechanical simulations predict that the ocular pulse induces oscillatory shear stress along Schlemm’s canal (SC) endothelium. SC cells release signalling factors, such as nitric oxide, in response to shear stress, which may affect outflow facility. We hypothesize that the ocular pulse modulates outflow facility by stimulating shear-induced production of nitric oxide from SC cells. This project examines the effect of IOP oscillations on outflow facility.
Using iPerfusion, we measured outflow facility whilst imposing 2-3 mmHg oscillations in IOP. We used post-mortem cadaveric C57BL/6 mice (13-14 weeks) with the eyes retained in situ, imposing sinusoidal oscillations at 10 Hz to mimic the murine heart rate. Oscillations were generated using iPulse, a custom-built oscillatory pressure module calibrated and tuned using a fine glass capillary and flexible tubing. Signal decomposition was used to isolate and measure the steady component of the dynamic flow rate entering the eye during oscillations. For experiments, one eye of 5 mice was cannulated following pentobarbital overdose and acclimated under steady conditions at 8 mmHg for 2 hours using PBS + 5.5 mM glucose, followed by 5-10 periods (20-30 minutes each) of alternating oscillatory or steady pressure.
We validated that iPulse can generate 10 Hz pressure oscillations of 2-3 mmHg whilst accurately measuring the resistance of a glass capillary that matched the resistance of a mouse eye. During acclimation at 8 mmHg, the baseline outflow facility (flow÷pressure) was 2.6 [1.9, 3.5] nl/min/mmHg (mean [95% CI]). During the oscillatory period, the average facility increased on average by 12 [4, 20] % (p<0.01) relative to the facility measured during the surrounding steady periods. The effect was reversible and disappeared soon after oscillations were halted (Figure).
The ocular pulse causes a rapid increase in outflow facility in mice. These studies reveal a dynamic component to outflow function that responds instantly to the ocular pulse and may be important for outflow regulation and IOP homeostasis. Future studies will examine the role of nitric oxide in the oscillatory response.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Outflow facility increases during the period of oscillations on (red) relative to periods of oscillations off (blue).
This PDF is available to Subscribers Only