Circadian IOP Rhythm in Rats Is Driven by Neural Signals From the Brain

Feb 25, 2026Investigative ophthalmology & visual science

Daily Eye Pressure Changes in Rats Are Controlled by Brain Signals

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Abstract

Rats exhibited a circadian (IOP) rhythm that peaked at night, with a reduction of up to 103% in IOP during subjective night after application.

Circadian IOP rhythm persisted in constant darkness, indicating a central circadian control mechanism.
Tetrodotoxin applied during subjective night reduced IOP in a dose-dependent manner, while having no effect during subjective day.
Interventions did not alter the baseline, amplitude, period, or phase of the IOP rhythm in constant darkness.
Superior cervical ganglionectomy resulted in the complete loss of circadian IOP rhythm, suggesting its reliance on sympathetic signals.

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PURPOSE: The purpose of this study was to establish the origin of the circadian (IOP) in the rat.

METHODS: IOP was continuously monitored via wireless telemetry in adult Brown-Norway rats. After entrainment to a light/dark (LD) cycle, one cohort was transitioned to constant darkness (DD), and (TTX) was applied at different times and concentrations during subjective day (SD) and night (SN). Another cohort underwent superior cervical ganglionectomy (SCGx) and thereafter was maintained in LD. Effects of interventions were quantified via mean IOP and cosinor estimation of rhythm properties.

RESULTS: All rats exhibited a pronounced circadian IOP rhythm that peaked during SN and persisted in DD. TTX had no effect during SD and reduced IOP during SN in a dose-dependent manner by up to 103% ± 15% of the nocturnal elevation. TTX had no effect on the IOP rhythm of the non-instilled contralateral eye. Rhythm baseline, peak-to-peak amplitude, period, and phase in DD averaged 9.5 ± 1.7 mm Hg, 4.9 ± 1.4 mm Hg, 24.0 ± 0.1 hour, and 2.3 ± 1.0 minute before TTX instillation and were unchanged afterward. IOP was not significantly different during SD and SN after SGCx, indicating complete knockout of the circadian IOP rhythm.

CONCLUSIONS: The IOP rhythm in rats is driven by sympathetic efferent signals from a central circadian clock. Ocular clocks and circulating humoral factors do not appear to contribute to rhythmogenesis. The neural pathway of circadian pressure control may be relevant to glaucoma pathophysiology.

Key numbers

103% ± 15%

Maximum Reduction with

reduced nocturnal elevation during subjective night.

Δ = 0.5 ± 0.3 mm Hg

Rhythm Abolition after SCGx

No significant difference in during subjective day and night after SCGx.

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Circadian IOP Rhythm in Rats Is Driven by Neural Signals From the Brain

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