Circadian rhythm of intraocular pressure.

Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na+/K+-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the β1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.