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(Investigative Ophthalmology and Visual Science. 2008;49:929-933.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0386

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

Makoto Aihara,1,2 James D. Lindsey,1 and Robert N. Weinreb1

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 {alpha}2A-, {alpha}2B-, or the {alpha}2C-adrenergic receptor subtypes in the mouse.

METHODS. A microneedle method was used to measure IOP in knockout mice lacking the {alpha}2A-, {alpha}2B-, or the {alpha}2C-receptor ({alpha}2A-R–/–, {alpha}2B-R–/–, {alpha}2C-R–/–), in wild-type mice of the {alpha}2B knockout strain ({alpha}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), {alpha}2A-R–/– (n = 10), {alpha}2B-R–/– (n = 8), {alpha}2B-R+/+ (n = 8), and {alpha}2C-R–/– (n = 10). In parallel experiments, eyes from the {alpha}2A-R–/–, {alpha}2B-R–/–, {alpha}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, {alpha}2A-R–/–, {alpha}2B-R–/–, {alpha}2B-R+/+, and {alpha}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, {alpha}2B-R–/–, {alpha}2B-R+/+, and {alpha}2C-R–/–: P < 0.01; {alpha}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 {alpha}2A-R–/–, {alpha}2B-R–/–,{alpha}2C-R–/–, or C57BL/6 mice.

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








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