Continuous measurement and control of intraocular pressure in normal and glaucomatous eyes

University Of South Florida, Tampa FL

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Abstract

PROJECT SUMMARY Understanding the regulation of intraocular pressure (IOP) is crucial in diagnosing and managing glaucoma, a leading cause of irreversible blindness characterized by preferential loss of retinal ganglion cell (RGC). One of the most potent regulators is the autonomic nervous system, which most glaucoma medicines target to achieve therapeutic IOP-lowering effects. Autonomic signals can modulate IOP rapidly by altering ocular blood flow and slowly by adjusting aqueous humor production and outflow. As a result, IOP fluctuates over a wide range of time scales. The importance of these fluctuations to glaucoma etiology and pathophysiology remains largely uncertain. Of interest to this project are circadian fluctuations in IOP that are controlled by the suprachiasmatic nucleus (SCN) in the brain. IOP telemetry studies in rats and other animals find that these rhythmic fluctuations can attain levels at night that would be glaucomatous if sustained throughout the day, and yet the eye continues to stay healthy. How can this be? More research is needed on the influence of the circadian system and environmental factors, such as light exposure, on the IOP dynamics of healthy and glaucomatous eyes. The proposed work utilizes one-of-a-kind technologies for measuring and manipulating IOP round-the-clock in awake free-moving animals as small as rats to investigate the hypothesis that daily IOP elevation is crucial for eye function. So important that recurrent disruption of circadian signals to the eye at night by light, and possibly other factors, pushes homeostatic mechanisms to raise IOP at unnatural times of day and that this abnormal activation may contribute to glaucoma onset or accelerate disease progression. The specific aims are to characterize light-driven changes in IOP rhythmicity and variability, the processes that mediate these changes, and their impact on eye health in rats. Insights gained from the work could inform the development of personalized treatment strategies or lighting regimens that optimize IOP control according to individual circadian profiles and uncover novel pathways for glaucoma intervention and vision preservation to explore in larger animals and humans.