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Jovi Chau-Yee Wong, Carina A Pothecary, Gareth T Banks, Mark W Hankins, Patrick M Nolan, Russell Foster, Stuart N Peirson; Melanopsin regulates circadian rhythms in contrast sensitivity but not pupillary light responses. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1980.
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© ARVO (1962-2015); The Authors (2016-present)
Melanopsin-expressing photosensitive retinal ganglion cells (pRGCs) mediate many non-image forming responses to light, including circadian entrainment and the pupillary light response (PLR). In addition, melanopsin is also required for circadian rhythms in the photopic electroretinogram (ERG), suggesting a role in retinal rhythms (Barnard et al., 2006). To determine if melanopsin plays a role in the regulation of other retinal circadian processes, here we investigate circadian rhythms in contrast sensitivity and the PLR in mice lacking melanopsin (Opn4-/-).
Optokinetic head tracking was used to measure contrast sensitivity using the OptoMotry system (Hwang et al., 2013) on wildtype mice (n=6) and Opn4-/- mice (n=5) under light/dark (LD) conditions (Zeitgeber time, ZT) at ZT6 and ZT18, and in constant darkness (Circadian time, CT) CT6 and CT18. PLR recordings were similarly performed on wildtype mice (n=6) and Opn4-/- mice (n=5) at ZT6, ZT18, CT6 and CT18, as described previously (Jagannath et al., 2015).
Contrast sensitivity was found to be dependent on melanopsin. Two-way ANOVA was performed. Wildtype mice exhibit significantly higher contrast sensitivity at ZT6 compared to ZT18 (p<0.0001), and at CT6 compared to CT18 (p<0.0001). Opn4-/- mice exhibit no significant difference between contrast sensitivity at ZT6 compared to ZT18 (p=0.26), nor CT6 compared to CT 18 (p=0.1746). By contrast, PLR circadian rhythms do not depend on melanopsin. Wildtype mice exhibited attenuated PLR at ZT18 compared to ZT6. Under constant conditions, the maximum pupil constriction was attenuated at CT18 compared to CT6. Opn4-/- mice also displayed similar differences in PLR, where the maximum pupillary constriction was attenuated at ZT18 compared to ZT6, and at CT18 compared to CT6. Two-way ANOVA statistical comparison of the maximum pupillary constriction between wildtype and Opn4-/- mice revealed a significant effect of genotype F(1, 56)=9.771, p=0.0028.
Here we report that melanopsin is necessary for circadian rhythms in contrast sensitivity, but not circadian rhythms in the PLR. This suggests that circadian regulation of these responses occurs via different mechanisms. Circadian regulation of contrast sensitivity, like photopic ERG, is dependent on melanopsin, suggesting regulation at the level of the retina. Rhythms in PLR may be regulated by central circadian neural mechanisms.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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