April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Analysis of Circadian Rhythm Gene Expression With Reference to Diurnal Variation of Intraocular Pressure (IOP) in Mice
Author Affiliations & Notes
  • Lauren A Dalvin
    Ophthalmology, Mayo Clinic, Rochester, MN
  • Michael P Fautsch
    Ophthalmology, Mayo Clinic, Rochester, MN
  • Footnotes
    Commercial Relationships Lauren Dalvin, None; Michael Fautsch, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5677. doi:
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      Lauren A Dalvin, Michael P Fautsch; Analysis of Circadian Rhythm Gene Expression With Reference to Diurnal Variation of Intraocular Pressure (IOP) in Mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5677.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The molecular basis for diurnal variation in IOP is not fully understood. We hypothesized that local expression of circadian rhythm clock genes in the iris-ciliary body complex may contribute to the 24-hour pattern of IOP. To assess our hypothesis, we evaluated the correlation of circadian rhythm gene expression for Per1, Per2, Clock, Bmal, Cry1 and Cry2 to diurnal IOP variation.

Methods: C57BL/6 mice (n=30) were acclimated to a 12-hour light-dark cycle for 7 days. Following acclimation, IOP of left and right eyes of each animal was measured for 5 consecutive days at Zeitgeber Times (ZT) 2, 6, 10, 14, 18, and 22 hours. On day 6 after initiation of IOP measurements, mice were sacrificed at ZT 2, 6, 10, 14, 18, and 22 (n=5 per group). Eyes were enucleated and flash-frozen. The iris-ciliary body complex was dissected and total RNA was extracted. Quantitative real-time PCR was performed to assess the expression of circadian rhythm genes at each ZT.

Results: IOP measurements confirmed a distinct 24-hour pattern, with IOP lowest at ZT 2 (15.20 ± 0.22 mmHg; the first measured time after lights on) and highest at ZT 14 (17.80 ± 0.13 mmHg; the first time after lights off). Peak expression for Per1, Per2, Cry1, and Cry2 occurred between ZT 10-14, while Clock and Bmal had troughs near those times. Gene expression levels were normalized to 18S ribosomal RNA and correlated with IOP. Linear regression analysis showed P-values of 0.01 (Per1), 0.005 (Per2), 0.0001 (Clock), 0.01 (Bmal), 0.01 (Cry1), and 0.07 (Cry2). Except Cry1, all gene expression changes were found to precede changes in IOP. For Cry1, highest gene expression occurred concurrently with highest measured IOP. Per1, Per2, Cry1, and Cry2 expression levels were directly related to IOP, while Clock and Bmal were inversely related.

Conclusions: Statistically significant correlations between Per1, Per2, Clock, Bmal, and Cry1 gene expression and IOP suggest that regulation of these clock genes may contribute to the daily circadian rhythm variation in IOP.

Keywords: 455 ciliary body • 458 circadian rhythms • 568 intraocular pressure  
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