Circadian IOP rhythm in rats is driven by neural signals from the brain

Intraocular pressure (IOP) exhibits a robust circadian rhythm whose driving mechanisms remain poorly defined. This study aimed to establish whether the circadian IOP rhythm in rats originates from local ocular oscillators or non-local neural or humoral inputs. IOP was monitored continuously in adult Brown Norway rats using an in-house telemetry system, and topical neurotoxin instillation and superior cervical ganglionectomy were performed. TTX produced a rapid, dose-dependent reduction of nocturnal IOP when applied during the dark phase but had no effect during the light phase. This hypotensive effect was unilateral, short-lived, and consistent with local sodium channel blockade of sympathetic efferents. In contrast, SCGx abolished the circadian rhythm entirely, eliminating the nocturnal IOP elevation. These findings demonstrate that the rat IOP rhythm is not generated by an intrinsic oscillator or circulating humoral signals but is instead driven by sympathetic efferent input from the superior cervical ganglion. These results highlight species-specific differences in the mechanisms of circadian IOP regulation and motivate future direct mechanistic studies on the IOP rhythm in relevant animal models of glaucoma.