Effect on diurnal intraocular pressure variation of eliminating the α-2 adrenergic receptor subtypes in the mouse

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.