Circadian rhythm of intraocular pressure in the adult rat

Abstract

Ocular hypertension is a risk factor for developing glaucoma, which consists of a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells and subsequent irreversible vision loss. Our understanding of how intraocular pressure damages the optic nerve is based on clinical measures of intraocular pressure that only gives a partial view of the dynamic pressure load inside the eye. Intraocular pressure varies over the course of the day and the oscillator regulating these daily changes has not yet been conclusively identified. The purpose of this study was to compare and contrast the circadian rhythms of intraocular pressure and body temperature in Brown Norway rats when these animals are housed in standard light-dark and continuous dim light (40–90 lux) conditions. The results from this study show that the temperature rhythm measured in continuous dim light drifted forward relative to external time, indicating that the rhythm was free running and being regulated by an internal biological clock. Also, the results show that there is a persistent, but dampened, circadian rhythm of intraocular pressure in continuous dim light and that the circadian rhythms of temperature and intraocular pressure are not synchronized by the same central oscillator. We conclude that once- or twice-daily clinical measures of intraocular pressure are insufficient to describe intraocular pressure dynamics. Similarly, our results indicate that, in experimental animal models of glaucoma, the common practice of housing animals in constant light does not necessarily eliminate the potential influence of intraocular pressure rhythms on the progression of nerve damage. Future studies should aim to determine whether an oscillator within the eye regulates the rhythm of intraocular pressure and to better characterize the impact of glaucoma on this rhythm.

Modeling glaucoma in rats by sclerosing aqueous outflow pathways to elevate intraocular pressure

“…In the light phase, the IOP in normal eyes measures approximately 20 mmHg by tonopen and TonoLab, while that during the dark is significantly increased to over 30 mmHg. (Kwong et al, 2013; Lozano et al, 2015; Moore et al, 1996; Valderrama et al, 2008) These considerations may apply to mice as well, as Liu has demonstrated higher IOP in the dark in mice monitored telemetrically. (Li and Liu, 2008) However, detailed assessment of this by non-invasive tonometry in awake mice has not yet been performed.…”

“…Fortunately, we have determined that, when animals are housed in a constant, low-light level environment (approximately 90 lux), the innate IOP fluctuation is suppressed. (Lozano et al, 2015; Morrison et al, 2005; Pang et al, 2005b) This maneuver, in addition to reducing one cause of IOP fluctuation, allows the researcher greater latitude on when to measure IOP.…”

MicroRNA Expression in the Glaucomatous Retina

“…Eight-month-old Brown Norway rats were housed in constant low-level light according to the standard protocol in our laboratory. This approach was adopted to attenuate circadian fluctuations of IOP 8,51 and to enable meaningful comparison with our previously published data using the same experimental glaucoma model housed in identical light conditions. 8,16,20,52 Aqueous outflow obstruction was created by injecting hypertonic saline unilaterally into episcleral veins, resulting in sustained elevation of IOP.…”

Ocular Clocks: Adapting Mechanisms for Eye Functions and Health

“… 19 – 21 They also include processes linked to retina survival such as rhythms in shedding of rod and cone outer segments and phagocytosis by the underlying RPE 22 , 23 and the vulnerability to phototoxicity. 24 In addition, rhythmic processes have been reported elsewhere in the eye, such as in the cornea (daily variation of thickness or mitotic rate 25 , 26 ) and in the ciliary body (aqueous production contributing to intraocular pressure 27 , 28 ). In line with these results, transcriptomics analysis of the eyes over the 24-hour period provided an extensive view of processes under cyclic control in ocular tissues.…”