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Rie Suzuki, Shu Matsushita, Osamu Sakai, Hideki Tokushige; The influence of reversed light-dark cycle on circadian rhythm of intraocular pressure in mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1066.
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© ARVO (1962-2015); The Authors (2016-present)
Circadian rhythm of intraocular pressure (IOP) shows a biphasic pattern in mice. It has been reported that constant light or dark exposure disrupted the biphasic pattern of IOP, suggesting that the presence or absence of ocular light stimulation is one of the key factors to control the circadian rhythm of IOP. However, the influence of reversal of light-dark cycle on the circadian rhythm of IOP remains to be clarified in mice. In this study, we examined the influence of reversal of light and dark cycle on circadian rhythm of IOP, and investigated the IOP-lowering effects of glaucoma drugs in this model.
C57BL6J mice were exposed to two different light-dark cycle, normal light-dark cycle (L/D cycle, turn on the light at 8AM, off at 8PM) and reversed light-dark cycle (D/L cycle, off at 10AM, on at 10PM). Before and 4, 7, 14, and 21days after light cycle change, IOP was measured immediately after turning on and off light. The effects of the glaucoma drugs; Latanoprost (LAT) and Timolol (TIM) during daytime (D) and nighttime (N) in the each light-dark cycle were evaluated.
In the L/D cycle mice, IOP showed a normal biphasic pattern (D; 17.4±0.2 mmHg, N; 24.1±0.3 mmHg). The reversed light-dark cycle disappeared the biphasic pattern of IOP at 4 days, and inverted the circadian rhythm of IOP at 21 day (D; 22.8±0.3 mmHg, N; 16.4±0.2 mmHg). In L/D cycle mice, LAT induced transient increase of IOP 1 hour after administration and then gradually reduced IOP in the daytime, but the transient increase of IOP by LAT was not observed during nighttime. TIM and LAT decreased IOP markedly stronger in the nighttime than in the daytime under L/D cycle. In contrast, the responses to these drugs in lowing IOP were inverted between daytime and nighttime under D/L cycle.
The reversed light-dark cycle inverted not only the circadian rhythm of IOP, but also the pattern in IOP-lowering effect of glaucoma drugs. The ocular light stimulation may be an important factor to control the circadian rhythm of IOP. Furthermore, during both nighttime under L/D cycle and daytime under D/L cycle, the effects of glaucoma drugs are potent compared with those during another period and, the transient IOP elevation by LAT, which was not shown in human, was not observed. IOP measurement in the daytime under D/L cycle could be useful option for evaluation of glaucoma drugs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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