Abstract
Purpose :
Most animal models of hypertensive glaucoma elevate pressure by experimentally disrupting aqueous drainage pathways, which alters the outflow facility and intraocular pressure (IOP) of the eye in an imprecise and unpredictable manner. This study presents the continued development of a micropump system capable of continuously measuring and controlling IOP through a cannula implanted in the anterior chamber. Furthermore, the device allows for repeated outflow facility measurement in conscious free-moving rats.
Methods :
The system is comprised of an implantable cannula and tether system, a pressure sensor, a micropump, and a flow restrictor. MATLAB was used to create a model of the eye and simulate the device to verify theory and optimize the feedback algorithm. The device pressure calibration and resistance were measured daily over a month to check for drift. Bench testing was conducted with an inline flow meter to verify flow rates produced by the device. The device was then tested on rats anesthetized with ketamine and xylazine using one of two paradigms (constant flow or feedback-controlled flow) to measure outflow facility. Finally, the system was deployed in an awake rat to demonstrate proof of concept.
Results :
The device showed no drift in flow-restrictor resistance, pressure generation, or pressure sensor readings over 30+ days when subjected to flow rates between 0 and 2 ul/min. It was bench tested with a small-diameter cannula and reported an outflow facility of 1.109 ± 0.041 ul/min/mmHg, which was not significantly different from the value of 1.134 ± 0.094 ul/min/mmHg measured using a commercial pump. MATLAB simulations indicated a feedback control algorithm would allow for over 5X faster measurements and later confirmed during testing in anesthetized animals. When tested on anesthetized rats utilizing the feedback algorithm, mean outflow facility was 0.0228 +/- 0.003 ul/min/mmHg as measured by the device and 0.0233 +/- 0.0032 ul/min/mmHg as measured with an inline flowmeter (N=14, p=0.29). In the awake animal (n=2) a diurnal rhythm was recorded, with outflow facility lowest at night (~0.01ul.min/mmHg) and highest during the day (~0.025 ul/min/mmHg).
Conclusions :
The system displayed reliability in outflow facility measurements over multiple weeks and can be used to study outflow facility in conscious freely-moving rats. The feedback algorithm provides an increased temporal resolution.
This is a 2021 ARVO Annual Meeting abstract.