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Effect on Diurnal Intraocular Pressure Variation of Eliminating the -2 Adrenergic Receptor Subtypes in the Mouse

¹From the Hamilton Glaucoma Center, University of California San Diego, La Jolla, California; and the ²Department of Ophthalmology, University of Tokyo, Tokyo, Japan.

PURPOSE. To investigate the effect on circadian variation of intraocular pressure (IOP) of eliminating the 2A-, 2B-, or the 2C-adrenergic receptor subtypes in the mouse.

METHODS. A microneedle method was used to measure IOP in knockout mice lacking the 2A-, 2B-, or the 2C-receptor (2A-R^–/–, 2B-R^–/–, 2C-R^–/–), in wild-type mice of the 2B knockout strain (2B-R^+/+), and in the background strain mice, C57BL/6. All mice were maintained in a 12-hour light–dark cycle commencing at 0600 hours. IOP was measured at 0900 and 2100 hours in the five groups: C57BL/6 (n = 8), 2A-R^–/– (n = 10), 2B-R^–/– (n = 8), 2B-R^+/+ (n = 8), and 2C-R^–/– (n = 10). In parallel experiments, eyes from the 2A-R^–/–, 2B-R^–/–, 2C-R^–/–, and C57BL/6 mice were embedded in epoxy resin, and semithin sections were stained with toluidine blue.

RESULTS. IOP at 0900 hours in B6, 2A-R^–/–, 2B-R^–/–, 2B-R^+/+, and 2C-R^–/– mice was 17.1 ± 1.8, 17.7 ± 1.4, 17.1 ± 2.1, 17.6 ± 1.3, and 17.3 ± 0.9 mm Hg, respectively (mean ± SD). IOP at 2100 hours in the same eyes was 19.6 ± 1.9, 19.2 ± 2.2, 20.5 ± 1.5, 19.7 ± 0.8, and 21.3 ± 2.7 mm Hg, respectively. There was no significant difference among these genotypes in IOP measured at either time point (P > 0.05, ANOVA). Within each genotype, IOP at 2100 hours was significantly higher than IOP at 0900 hours (C57BL/6, 2B-R^–/–, 2B-R^+/+, and 2C-R^–/–: P < 0.01; 2A-R^–/–: P < 0.05, paired t-test). Differences in the diurnal IOP change among the different genotypes were insignificant (P > 0.05, ANOVA). Histopathologic assessment found minimal differences in the structural organization of the anterior segment among the 2A-R^–/–, 2B-R^–/–,2C-R^–/–, or C57BL/6 mice.

CONCLUSIONS. These results indicate that IOP magnitude and circadian variation are minimally altered by the absence of the 2A-, 2B-, or 2C-receptor subtypes in transgenic mice.

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