The Retinal Circadian Clock and Photoreceptor Viability

Abstract

Circadian rhythms are present in most living organisms, and these rhythms are not just a consequence of the day/night fluctuation, but rather they are generated by endogenous biological clocks with a periodicity of about 24 h. In mammals, the master pacemaker of circadian rhythms is localized in the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN controls circadian rhythms in peripheral organs. The retina also contains circadian clocks which regulate many aspects of retinal physiology, independently of the SCN. Emerging experimental evidence indicates that the retinal circadian clocks also affect ocular health, and a few studies have now demonstrated that disruption of retinal clocks may contribute to the development of retinal diseases. Our study indicates that in mice lacking the clock gene Bmal1, photoreceptor viability during aging is significantly reduced. Bmal1 knockout mice at 8-9 months of age have 20-30% less nuclei in the outer nuclear layer. No differences were observed in the other retinal layers. Our study suggests that the retinal circadian clock is an important modulator of photoreceptor health.

Keywords: Aging; Cell viability; Circadian rhythm; Clock genes; Cone; Knockout mice; Oscillation; Photoreceptors; Retinal degeneration.

Fig. 1

Morphometric analysis of retinae obtained from young (3 months old, black bars) and old (8 months old, white bars) of control, Bmal1^−/− and Clock^−/−/Npas2^−/− (Cl/Np2) mice. The number of cells in the ONL of 8 months old Bmal1 (B) and Clock/Npas2 KOs (D) were significantly lower than the number of cells in 3 months old mice (A, C) of the same genotype (One-way ANOVA following post hoc test * p< 0.05) and age matched control group (^# p<0.05). No differences in the number of cells were observed in the INL and/or GCL (n= 3-4). The number of cells in the ONL of young Bmal1 and Clock/Npas2 KO mice was not different from the number of cells in control mice of the same genotype (C57BL/6). The microphotographs in A, B, C and D represent a typical example of a section obtained from 3 months old Bmal1 KO (A), 8 months old Bmal1 KO (B), 3 months old Clock/Npas2 KO (C) and 8 months old Clock/Npas2 KO (D).