Fig. 1

Regulatory pathways of IOP rhythm by the SCN and hypothesis model of aqueous humor inflow in mice. Regulatory pathways of the IOP rhythm by the SCN through the adrenal glucocorticoid and sympathetic nerve pathways and an anatomical model. The circadian timing signals of the NE and GC are mainly transmitted to the trabecular meshwork cells (TM) and ciliary epithelium (pars plana and pars plicata, respectively) for aqueous humor production, which seems to be independent of the ciliary clock. The aqueous humor is drained via two pathways: trabecular and uveoscleral outflows. However, the molecular mechanisms underlying the circadian regulation of aqueous humor production and drainage remain unclear. In nonpigmented epithelial (NPE) cells, Na⁺/K⁺ATPase (NKA) may mainly contribute to AH inflow rhythm formation via nocturnal β2-adrenergic receptor (AR; Abrb2)-mediated cAMP accumulation, which may generate nocturnal IOP increase. The role of GC, with an evening peak in rodents, in AH inflow rhythm formation remains unclear; this may be mediated by the cAMP-related membrane GC receptor (GR) or nuclear receptor GR. This figure is modified from a previous study [20]