Researchers uncover cause of nighttime eye pressure spikes

Intraocular pressure is the largest risk factor for glaucoma and fluctuates greatly throughout the day. However, even though diurnal humans and nocturnal mice have opposite biological rhythms, it is known that intraocular pressure becomes high at night in both. The mechanism has been unknown for many years. Also, it is known that the intraocular pressure rhythm changes with aging, but there has been no theory that can explain these in a unified way. A research group including Associate Professor Keisuke Ikegami of the Graduate School of Bioresource and Bioenvironmental Sciences at Kyushu University proposed a new mathematical model explaining that the daily fluctuation of intraocular pressure is caused by the overlapping of two biological signals: glucocorticoids secreted from the adrenal gland and noradrenaline released from the sympathetic nerve. The study was published in npj Biological Timing and Sleep.

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Glucocorticoids have different peak secretion times in diurnal animals and nocturnal animals. On the other hand, noradrenaline is thought to work strongly at night in both animals. The research group showed that by adding these two temporal waves together, the phenomenon where intraocular pressure becomes high at night can be explained in both diurnal humans and nocturnal mice. Furthermore, they measured the intraocular pressure of young mice and aged mice every 4 hours and analyzed the changes in the intraocular pressure rhythm due to aging.

As a result, in aged mice, the peak time of the intraocular pressure rhythm shifted earlier, and the daily fluctuation tended to become smaller. In mice where part of the sympathetic nerve going to the eye was removed, changes in the intraocular pressure rhythm very similar to those in the aged mice were also seen.

This result shows the possibility that a decrease in sympathetic nerve signals is involved in the changes in the intraocular pressure rhythm due to aging. Furthermore, when they analyzed previously reported human data, they found that changes in the intraocular pressure rhythm with aging can also be explained by this model. In other words, the model proposed this time showed the possibility that not only the species difference between humans and mice but also the changes due to aging can be explained within a single framework. This indicated a new view that the daily fluctuation of intraocular pressure is not determined by a single mechanism, but is formed by the temporal overlapping of multiple biological signals.

This research is a fundamental study intended to propose a theoretical model for explaining daily fluctuation of intraocular pressure. It will not translate into immediate clinical applications. However, looking ahead five to ten years, this model holds promise for tailoring personalized glaucoma care to individual patients.

In current clinical practice, intraocular pressure is typically measured during limited daytime visiting hours. However, since intraocular pressure fluctuates around the clock, many patients likely experience dangerous spikes outside of clinic hours that go unnoticed. If this model develops, there is a possibility that a patient's 24-hour intraocular pressure fluctuation can be estimated from a small number of intraocular pressure measurements or hormone information in blood and saliva.

The research group aims to improve the accuracy of the model in the future by verifying the relationship between time-series data of cortisol (a glucocorticoid) and autonomic nerve activity in humans and intraocular pressure fluctuations. They also plan to advance analysis on the effects that disturbances of the body clock caused by sleep disorders, aging, shift work, etc., have on the intraocular pressure rhythm. Furthermore, for glaucoma therapeutic drugs such as beta-blockers and prostaglandin-related drugs, application to chronotherapy, which predicts the time of day when administration is most effective, is also expected.

In the future, it may lead to the development of personalized treatment based on the circadian rhythm of each patient and diagnostic technology useful for early evaluation of glaucoma onset risk.

Ikegami commented, "Until now, we have clarified that glucocorticoids and the sympathetic nerve are each involved in the daily fluctuation of intraocular pressure. In this research, by integrating them into a single framework, we showed that the difference between humans and mice, and the changes due to aging can be explained. We want to further develop intraocular pressure rhythm research and connect it to new diagnosis and treatment methods for glaucoma."

Journal Information
Publication: npj Biological Timing and Sleep
Title: Additive framework of hormonal waves accounts for species and age differences in circadian intraocular pressure rhythm
DOI: 10.1038/s44323-026-00096-y