title: The Role of Beta-Adrenergic Receptors in the Regulation of Circadian Intraocular Pressure Rhythm in Mice.
abstract: To investigate whether the elimination of β1- and β2-adrenergic receptors alters the diurnal intraocular pressure (IOP) rhythm in mice.
  
  
  
  β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice were anesthetized intraperitoneally, with their IOPs measured via microneedle method. After entrainment to a 12-h light-dark (LD) cycle (light phase 6:00-18:00), IOPs were measured every 3 h from 9:00 to 24:00 (group 1, β1-/β2-adrenergic receptor double-knockout mice, n = 11; C57BL/6J, n = 15). The IOP measurements at 15:00 and 24:00 under a 12-h LD cycle and in the constant darkness (1 day and 8 days after exposure to darkness, respectively) were performed in another group of β1-/β2-adrenergic receptor double-knockout mice (group 2, n = 12). IOP variance throughout the day and mean IOP differences among time points were evaluated using a linear mixed model.
  
  
  
  β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice showed biphasic IOP curves, low during the light phase and high during the dark phase; the fluctuation was significant (P < 0.001). The peak IOP (18.7 ± 1.4 mmHg) occurred at 24:00 and the trough IOP (13.5 ± 1.5 mmHg) occurred at 15:00 in β1-/β2-adrenergic receptor double-knockout mice group. IOP curves of β1-/β2-adrenergic receptor double-knockout and C57BL/6J were nearly parallel, and the IOPs of β1-/β2-adrenergic receptor double-knockout mice were significantly higher than those of C57BL/6J mice (P < 0.001). Under constant dark (DD) conditions, IOP at 24:00 (18.1 ± 1.5 mmHg) was significantly higher than that at 15:00 (13.3 ± 1.2 mmHg) (P < 0.001). The transition from the LD cycle to DD environment produced no significant change in IOP (P = 0.728).
  
  
  
  Elimination of both β1- and β2-adrenergic receptors did not disturb the biphasic diurnal IOP rhythm in mice.
authors.affiliation: a Department of Ophthalmology and Visual Science , Kanazawa University Graduate School of Medical Science , Kanazawa , Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: a Department of Ophthalmology and Visual Science , Kanazawa University Graduate School of Medical Science , Kanazawa , Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Higashide
authors.affiliation: b Department of Anatomy , Kawasaki Medical School , Kurashiki , Japan.|c Research Center for Ultra-High Voltage Electron Microscopy , Osaka University , Ibaraki , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toida
authors.affiliation: a Department of Ophthalmology and Visual Science , Kanazawa University Graduate School of Medical Science , Kanazawa , Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013562:Sympathectomy
chemical_list: D011943:Receptors, Adrenergic, beta
keywords: circadian rhythm; double-knockout mice; intraocular pressure; microneedle method; β-adrenergic receptor