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E. Murotani, Y. Gao, M. Sakurai, H. Takeda, T. Higashide, K. Toida, K. Sugiyama; Effects of Elimination of β1/β2-Adrenergic Receptors on Circadian Intraocular Pressure Rhythm. Invest. Ophthalmol. Vis. Sci. 2010;51(13):572.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether the elimination of both β1- and β2-adrenergic receptors alters the diurnal intraocular pressure (IOP) rhythm in mice.
β1- and β2-adrenergic receptor double-knockout mice (β1β2ADR-/-) and C57BL/6J mice were anesthetized intraperitonealy with ketamine (100 mg/kg) and xylazine (9 mg/kg). IOP was measured by a microneedle method. After entrainment to 12 hr light-dark cycle (light phase 6:00-18:00) more than 2 weeks, IOPs were measured every 3 hour from 9:00 to 24:00 (group 1, β1β2ADR-/-, n=11; C57BL/6J, n=2-7 at each time point). Another group of β1β2ADR-/- mice (group 2, n=12) were entrained initially to 12 hr light-dark cycle, subsequently to 24 hr constant dark environment more than 2 weeks. IOPs were measured at 15:00 and 24:00 before and after the period of constant dark. In parallel experiments, eyes were enucleated after perfusion fixation. Histopathologic examinations were performed at both the light and electron microscopic levels.
β1β2ADR-/- mice showed a biphasic IOP curve, low during the light phase and high during the dark phase. The fluctuation was significant by Friedman rank sum test (p<0.001). The peak IOP (18.7±1.4 mmHg, mean ± standard deviation) occured at 24:00 and the trough IOP (13.5±1.5 mmHg) at 15:00. The mean difference of IOP between 15:00 and 24:00 was 5.2±1.3 mmHg. The IOP curve of β1β2ADR-/- was nearly parallel to that of C57BL/6J and higher by 1 to 3 mmHg. Under constant dark conditions, IOP at 24:00 (18.1±1.5 mmHg) was significantly higher than IOP at 15:00 (13.3±1.2 mmHg) (Wilcoxon signed rank test, p<0.001). Transition from 12 hr light-dark cycle to 24 hr constant dark environment did not produce a significant change in IOP (Mann-Whitney U-test, p=0.34, 15:00; p=0.36, 24:00). No histological abnormality was detected in the ciliary body of β1β2ADR-/- mice.
The elimination of both β1- and β2-adrenergic receptors did not disturb biphasic diurnal IOP rhythm.
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