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PURPOSE: To investigate the effect on circadian variation of intraocular pressure (IOP) of eliminating the α2A-, α2B-, or the α2C-adrenergic receptor subtypes in the mouse. METHODS: A microneedle method was used to measure IOP in knockout mice lacking the α2A-, α2B-, or the α2C-receptor (α2A-R-/-, α2B-R-/-, α2C-R-/-), in wild-type mice of the α2B knockout strain (α2B-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), α2A-R-/- (n = 10), α2B-R-/- (n = 8), α2B-R+/+ (n = 8), and α2C-R-/- (n = 10). In parallel experiments, eyes from the α2A-R-/-, α2B-R-/-, α2C-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, α2A-R-/-, α2B-R-/-, α2B-R+/+, and α2C-R-/- mice was 17.1 ± 1.8, 17.7 ± 1.4, 17.1 ± 2.1, 17.6 ± 1.3, and 17.3 ± 0.9 mmHg, 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 mmHg, 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, α2B-R-/-, α2B-R+/+, and α2C-R-/-: P < 0.01; α2A-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 α2A-R-/-, α2B-R-/-,α2C-R-/-, or C57BL/6 mice. CONCLUSIONS: These results indicate that IOP magnitude and circadian variation are minimally altered by the absence of the α2A-, α2B-, or α2C-receptor subtypes in transgenic mice.
Dr. M. Aihara, Hamilton Glaucoma Center, University of California San Diego, La Jolla, CA, USA
6.1.2 Fluctuation, circadian rhythms (Part of: 6 Clinical examination methods > 6.1 Intraocular pressure measurement; factors affecting IOP)
11.3 Adrenergic drugs (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.8 Pharmacology (Part of: 3 Laboratory methods)