A portable feedback-controlled pump for monitoring eye outflow facility in conscious rats

Abstract

Intraocular pressure (IOP) is heavily influenced by the resistance of trabecular outflow pathways through which most of the aqueous humor produced by the eye continuously drains. The standard method of quantifying outflow resistance and other aspects of ocular fluid dynamics is eye cannulation, which allows for direct measurement and manipulation of IOP and flow in animal models. Since the method is invasive, indirect techniques that are slower and less accurate must be used for chronological studies. A novel technology is introduced that can autonomously measure outflow facility in conscious rats multiple times a day. A smart portable micropump infuses fluid into the eye through a permanently-implanted cannula and dynamically adjusts flow rate using a unique proportional feedback algorithm that sets IOP to a target level, even though IOP fluctuates erratically in awake free-moving animals. Pressure-flow data collected by the system from anesthetized rats were validated against intraocular recordings with commercial pressure and flow sensors. System and sensor estimates of outflow facility were indistinguishable, averaging 23 ± 3 nl·min-1·mmHg-1 across animals (n = 11). Pressure-flow data were then collected round-the-clock for several days from conscious rats, while outflow facility was measured every few hours. A significant diurnal facility rhythm was observed in every animal (n = 4), with mean daytime level of 22 ± 10 nl·min-1·mmHg-1 and mean nighttime level of 15 ± 7 nl·min-1·mmHg-1. The rhythm correlated with diurnal changes in IOP and likely contributed prominently to those changes based on the day-night swing in facility magnitude. Hence, the portable smart pump offers a unique tool for repeated long-term monitoring of outflow facility and other possible parameters of ocular health. It could also be useful in animal glaucoma studies for reversibly inducing acute or chronic ocular hypertension without explicitly damaging trabecular outflow pathways.