Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice.
Keisuke IkegamiSatoru MasubuchiPublished in: Communications biology (2022)
Intraocular pressure (IOP) is an important factor in glaucoma development, which involves aqueous humor (AH) dynamics, with inflow from the ciliary body and outflow through the trabecular meshwork (TM). IOP has a circadian rhythm entrained by sympathetic noradrenaline (NE) or adrenal glucocorticoids (GCs). Herein, we investigated the involvement of GC/NE in AH outflow. Pharmacological prevention of inflow/outflow in mice indicated a diurnal outflow increase, which was related to TM phagocytosis. NE showed a non-self-sustained inhibition in phagocytosis of immortalized human TM cells, but not GC. The pharmacological and reverse genetic approaches identified β1-adrenergic receptor (AR)-mediated exchange proteins directly activated by cyclic adenosine monophosphate (EPAC)-SHIP1 signal activation by ablation of phosphatidylinositol triphosphate, regulating phagocytic cup formation. Furthermore, we revealed the phagocytosis involvement in the β1-AR-EPAC-SHIP1-mediated nocturnal IOP rise in mice. These suggest that TM phagocytosis suppression by NE can regulate IOP rhythm through AH outflow. This discovery may aid glaucoma management.
Keyphrases
- high fat diet induced
- blood pressure
- endothelial cells
- obstructive sleep apnea
- bone mineral density
- atrial fibrillation
- heart rate
- gene expression
- type diabetes
- single cell
- wild type
- insulin resistance
- skeletal muscle
- protein kinase
- genome wide
- metabolic syndrome
- dna methylation
- mass spectrometry
- cell death
- high resolution
- oxidative stress
- optical coherence tomography
- postmenopausal women
- gas chromatography
- binding protein
- atomic force microscopy