Abstract
Purpose :
Telemetry measurements of intraocular pressure (IOP) have revealed a circadian IOP rhythm associated with the ambient light-dark cycle. To elucidate the governing mechanisms of the rhythm, efferent nerve activity was pharmacologically blocked to determine if the diurnal IOP variations originate in the eye or brain.
Methods :
All experiments were done on male, retired breeder Brown Norway rats housed under a 12-hr light/12-hr dark cycle. IOP was continuously recorded in awake free-moving rats by a custom wireless pressure sensor worn on the animal’s back that was connected to one eye by a cannula implanted into the anterior chamber. Animals were placed in constant dark 3 days after surgery and kept in darkness for 1 week prior to determine their free-running period before drug application. Animals were then briefly anesthetized with isoflurane 1 hr prior to subjective night, and the implanted eye was instilled with a 10ml drop of either tetrodotoxin (TTX, 1mg/ml) or saline as a control. TTX effects were quantified in terms of time-to-peak (TTP) of the nighttime response, which was defined as the time IOP reached the mean nighttime level (8PM-4AM) prior to drug application, and area-under-the-curve (AUC) preceding and following the TTP with drug application.
Results :
Corneal instillation of TTX altered the nighttime IOP response on every trial (n=5), whereas saline had no effect. Nighttime TTP was significantly delayed by 5.2 ± 1.1 hrs (p<0.01), and nighttime AUC pre-TTP was significantly reduced by -24.1 ± 11.5 % (p<0.05). Nighttime AUC post-TTP was not measurably different (-7.5 ± 15.2 %, p=0.25). No TTX effect was noted on the nighttime response in subsequent days.
Conclusions :
The delay in TTP indicates that TTX temporarily blocks spike-dependent neural signals that initiate nighttime elevation of IOP. These signals likely originate in the brain because the iridocorneal angle is innervated by efferent nerve fibers and the circadian clock mediating IOP rhythmicity was not permanently shifted in phase by corneal application of TTX.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.