Aqueous Humor Dynamics of the Brown-Norway Rat.

Purpose: The study aimed to provide a quantitative description of aqueous humor dynamics in healthy rat eyes. Methods: One eye of 26 anesthetized adult Brown-Norway rats was cannulated with a needle connected to a perfusion pump and pressure transducer. Pressure-flow data were measured in live and dead eyes by varying pump rate (constant-flow technique) or by modulating pump duty cycle to hold intraocular pressure (IOP) at set levels (modified constant-pressure technique). Data were fit by the Goldmann equation to estimate conventional outflow facility (C) and unconventional outflow rate (Fun). Parameter estimates were respectively checked by inserting a shunt of similar conductance into the eye and by varying eye hydration methodology. Results: Rat IOP averaged 14.6 ± 1.9 mm Hg at rest. Pressure-flow data were repeatable and indistinguishable for the two perfusion techniques, yielding C = 0.023 ± 0.002 µL/min/mm Hg and Fun = 0.096 ± 0.024 µL/min. C was similar for live and dead eyes and increased upon shunt insertion by an amount equal to shunt conductance, validating measurement accuracy. At 100% humidity Fun dropped to 0.003 ± 0.030 µL/min. Physiological washout was not observed (-0.35 ± 0.65%/h), and trabecular anatomy looked normal. Conclusions: Rat aqueous humor dynamics are intermediate in magnitude compared to those in mice and humans, consistent with species differences in eye size. C does not change with time or death. Evaporation complicates measurement of Fun even when eyes are not enucleated. Absence of washout is a notable finding seen only in mouse and human eyes to date.

A Wireless Pressure Sensor for Continuous Monitoring of Intraocular Pressure in Conscious Animals.

An important aspect of eye health in humans and animal models of human diseases is intraocular pressure (IOP). IOP is typically measured by hand with a tonometer, so data are sparse and sporadic and round-the-clock variations are not well characterized. Here we present a novel system for continuous wireless IOP and temperature measurement in small animals. The system consists of a cannula implanted in the anterior chamber of the eye connected to pressure sensing electronics that can be worn by rats or implanted in larger mammals. The system can record IOP with 0.3 mmHg accuracy and negligible drift at a rate of 0.25 Hz for 1-2 months on a regulated battery or indefinitely at rates up to 250 Hz via RF energy harvesting. Chronic recordings from conscious rats showed that IOP follows a diurnal rhythm, averaging 16.5 mmHg during the day and 21.7 mmHg at night, and that the IOP rhythm lags a diurnal rhythm in body temperature by 2.1 h. IOP and body temperature fluctuations were positively correlated from moment-to-moment as well. This technology allows researchers to monitor for the first time the precise IOP history of rat eyes, a popular model for glaucoma studies.

Development of a Smart Pump for Monitoring and Controlling Intraocular Pressure.

Animal models of ocular hypertension are important for glaucoma research but come with experimental costs. Available methods of intraocular pressure (IOP) elevation are not always successful, the amplitude and time course of IOP changes are unpredictable and irreversible, and IOP measurement by tonometry is laborious. Here we present a novel system for monitoring and controlling IOP without these limitations. It consists of a cannula implanted in the anterior chamber of the eye, a pressure sensor that continually measures IOP, and a bidirectional pump driven by control circuitry that can infuse or withdraw fluid to hold IOP at user-desired levels. A portable version was developed for tethered use on rats. We show that rat eyes can be cannulated for months without causing significant anatomical or physiological damage although the animal and its eyes freely move. We show that the system measures IOP with <0.7 mmHg resolution and <0.3 mmHg/month drift and can maintain IOP within a user-specified window of desired levels for any duration necessary. We conclude that the system is ready for cage- or bench-side applications. The results lay the foundation for an implantable version that would give glaucoma researchers unprecedented knowledge and control of IOP in rats and potentially larger animals.