Abstract
Purpose :
Recent work has established that the circadian nocturnal rise in intraocular pressure (IOP) seen in rats is regulated by the autonomic nervous system. To elucidate the governing mechanisms of the circadian IOP rhythm, β-adrenergic receptors were pharmacologically blocked to determine their role in this IOP elevation.
Methods :
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 ambulatory rats by a wireless pressure sensor worn on the animal’s back connected to one eye by a cannula implanted into the anterior chamber. After a 7-day recovery period and prior to drug application, animals were placed in constant darkness for 3 days to establish the free-running period of their IOP rhythm. Animals were then lightly anesthetized with isoflurane during either their subjective day (SD) or subjective night (SN), and the implanted eye was instilled with one drop of Timolol (0.5%) or saline as a control. IOP following Timolol instillation was compared to mean IOP 1-hr prior to instillation and mean IOP between 10AM-2PM on previous SD. Paired, one-tailed t-tests (α = 0.05, Shapiro-Wilk normality test) were used for statistical analysis.
Results :
When instilled during SN (n=3), Timolol significantly reduced IOP by 8.92 ± 4.71 mmHg (p<0.05) to a value not markedly different than SD IOP (p=0.36). Interestingly, when Timolol was instilled during SD (n=5), IOP was not measurably different than IOP on the previous SD (p=0.35). No Timolol effects were observed on the circadian IOP rhythm in subsequent days.
Conclusions :
The IOP reduction caused by Timolol instillation during SN suggests that β-adrenergic activation is required to produce nocturnal IOP elevation. In contrast, it appears that β-adrenergic receptors do not contribute to the mechanism that maintains baseline IOP during SD. Further, β-adrenergic receptors do not appear to play a role in the entrainment of the IOP circadian rhythm because no effect was observed on subsequent days.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.