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Circadian Intraocular Pressure Rhythm Is Generated by Clock Genes

¹From the Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; the ²Department of Anatomy and Cell Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; the ³Radiation Biology Center, Kyoto University, Kyoto, Japan; and the ⁴Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.

PURPOSE. The present study in a mouse model was undertaken to reveal the role of the circadian clock genes Cry1 and Cry2 in generation of 24-hour intraocular pressure (IOP) rhythm.

METHODS. IOP was measured at eight time points daily (circadian time [CT] 0, 3, 6, 9, 12, 15, 18, and 21 hours), using a microneedle method in four groups of C57BL/6J mice (groups 1 and 3, wild-type; groups 2 and 4, Cry-deficient [Cry1^–/–Cry2^–/–]). During the IOP measurements, mice in groups 1 and 2 were maintained in a 12-hour light–dark cycle (LD), whereas mice in groups 3 and 4 were kept in a constant darkness (DD) that started 24 to 48 hours before the measurements. Circadian IOP variations in each group were evaluated by one-way analysis of variance (ANOVA) and Scheffé tests.

RESULTS. In wild-type mice living in LD conditions, pressures measured in the light phase were significantly lower than those in the dark phase. This daily rhythm was maintained under DD conditions with low pressure in the subjective day and high pressure in the subjective night. In contrast, Cry-deficient mice did not show significant circadian changes in IOP, regardless of environmental light conditions.

CONCLUSIONS. These findings demonstrate that clock oscillatory mechanisms requiring the activity of core clock genes are essential for the generation of a circadian rhythm of intraocular pressure.

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