Effect of inhalation anesthesia with isoflurane on circadian rhythm of murine intraocular pressure

Abstract

Purpose: For research on circadian intraocular pressure (IOP), rebound tonometers are widely used with or without general anesthesia as a non-invasive approach to obtain IOP values. However, whether general anesthesia such as inhalation anesthesia with isoflurane affects the circadian rhythm of IOP and in turn IOP measurements is currently unclear. As such, data reporting IOP values obtained under general anesthesia should be interpreted with caution. The purpose of this study was to evaluate how general anesthesia with isoflurane inhalation affects the circadian rhythm of IOP.

Methods: C57Bl/6J strain mice maintained using a 12h:12h light/dark cycle (lights on and off at ZT0 and ZT12, respectively) were used. IOPs were measured using a rebound tonometer (Icare TonoLab) before and 3, 5, 10, 15, and 30 min after initiating anesthesia in both light and dark phases (ZT 2-6 and ZT 14-18, respectively). Awake IOPs and IOPs at 3 and 5 min after anesthesia initiation were also obtained at ZT5, 8, 11, 14, 17, and 20 to assess IOP diurnal curves under gas anesthesia.

Results: IOP values gradually decreased after anesthesia initiation in both light and dark phases (P < 0.001) and there was no interaction between light/dark phase and anesthesia time (P = 0.88). There was a slight, but not significant, reduction in IOP 3 min after initiating anesthesia (P = 0.23), and significant decreases in IOP occurred at subsequent timepoints (P ≤ 0.001). Both awake and anesthetized mice showed a robust IOP rhythm that reached a peak and trough in the dark and light phase, respectively. Awake IOP levels did not significantly differ from those for anesthetized mice at 3 min after anesthesia initiation at all time points (P ≥ 0.07).

Conclusions: Both awake and anesthetized mice demonstrated a robust circadian rhythm for IOP. Murine IOP showed similar gradual decreases under inhalation anesthesia with isoflurane in both the light and dark phases. IOPs measured using a rebound tonometer within 3 min of initiating isoflurane anesthesia were comparable to awake IOPs, and thus may be useful to monitor the circadian rhythm of IOP in mice.

Keywords: Circadian rhythm; Gas anesthesia; Intraocular pressure; Isoflurane; Mice.