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

Purpose: The purpose of this study was to establish the origin of the circadian intraocular pressure (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 tetrodotoxin (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.