Effect on diurnal intraocular pressure variation of eliminating the alpha-2 adrenergic receptor subtypes in the mouse.
OBJECTIVE
To investigate the effect on circadian variation of intraocular pressure (IOP) of eliminating the alpha2A-, alpha2B-, or the alpha2C-adrenergic receptor subtypes in the mouse.


METHODS
A microneedle method was used to measure IOP in knockout mice lacking the alpha2A-, alpha2B-, or the alpha2C-receptor (alpha2A-R(-/-), alpha2B-R(-/-), alpha2C-R(-/-)), in wild-type mice of the alpha2B knockout strain (alpha2B-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), alpha2A-R(-/-) (n = 10), alpha2B-R(-/-) (n = 8), alpha2B-R(+/+) (n = 8), and alpha2C-R(-/-) (n = 10). In parallel experiments, eyes from the alpha2A-R(-/-), alpha2B-R(-/-), alpha2C-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, alpha2A-R(-/-), alpha2B-R(-/-), alpha2B-R(+/+), and alpha2C-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, alpha2B-R(-/-), alpha2B-R(+/+), and alpha2C-R(-/-): P < 0.01; alpha2A-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 alpha2A-R(-/-), alpha2B-R(-/-),alpha2C-R(-/-), or C57BL/6 mice.


CONCLUSIONS
These results indicate that IOP magnitude and circadian variation are minimally altered by the absence of the alpha2A-, alpha2B-, or alpha2C-receptor subtypes in transgenic mice.
Aihara
Makoto
M
Hamilton Glaucoma Center, University of California San Diego, La Jolla, California 92093-0946, USA.
Lindsey
James D
JD
Weinreb
Robert N
RN
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D005838:Genotype; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015398:Signal Transduction; D014065:Tonometry, Ocular
C547769:Adra2a protein, mouse; C547772:Adra2b protein, mouse; C547775:Adra2c protein, mouse; D018341:Receptors, Adrenergic, alpha-2