Aging Alters Circadian Rhythms in the Mouse Eye

Abstract

The eye contains a circadian system that acts independently from the master circadian clock located in the brain. This circadian system regulates important physiological functions within the eye. Emerging experimental evidence also indicates that disruption of the ocular circadian clock, or its outputs, negatively affects the overall health of the eye. Although previous studies have investigated the effect of aging on the regulation of circadian rhythms, no study has investigated the effects of aging on the circadian rhythm in the ocular system. The aim of the present study was to investigate how aging affects the circadian rhythm of PER2::LUC bioluminescence in the retina, retinal pigment epithelium (RPE), and cornea. Our data suggest that among the 3 different ocular tissues investigated, the retina appears to be the most affected by aging whereas the RPE and cornea are less affected by aging. Our data, along with studies of other organs and tissues, suggest that reduction in the amplitude of rhythms is probably the most severe effect of aging on the circadian clock.

Keywords: PER2::LUC; RPE; aging; bioluminescence; circadian rhythm; cornea; retina.

Figure 1.

(A) Representative PER2::LUC bioluminescence rhythm in the cornea, retina and RPE dissected from young (3 months (mo.) old; black lines) and old (12 months old; grey lines) mice. (B) PER2::LUC rhythm of old retina showed an approximately 8.5 hrs. of phase-advance and RPE showed a slight delay in old mice. Black diamonds represent data obtained from young mice and grey diamonds represent data obtained from old mice (Mean ± SEM, n=6–10, * p<0.05, ** p<0.01, t-test). White and black bars above the plots indicate the light/dark cycle at which mice were exposed before preparation of organ cultures. (C) The period of PER2::LUC rhythm recorded from old retinas were approximately 2 hrs. longer than those observed in young mice (Mean ± SEM, n=6–10, ** p<0.01, t-test). Black bars represent young mice and grey bars represent old mice. (D) The cornea was the only tissue in which the rhythmic power of PER2::LUC circadian rhythm was affected by aging (Mean ± SEM, n=6–10, ** p<0.01, t-test). Black bars represent young mice and grey bars represent old mice.