The Visual Input Stage of the Mammalian Circadian Pacemaking System: I. Is There a Clock in the Mammalian Eye?

Abstract

Threads of evidence from recent experimentation in retinal morphology, neurochemistry, electrophysiology, and visual perception point toward rhythmic ocular processes that may be integral components of circadian entrainment in mammals. Components of retinal cell biology (rod outer-segment disk shedding, inner-segment degradation, melatonin and dopamine synthesis, electrophysiological responses) show self-sustaining circadian oscillations whose phase can be controlled by light-dark cycles. A complete phase response curve in visual sensitivity can be generated from light-pulse-induced phase shifting. Following lesions of the suprachiasmatic nuclei, circadian rhythms of visual detectability and rod outer-segment disk shedding persist, even though behavioral activity becomes arrhythmic. We discuss the converging evidence for an ocular circadian timing system in terms of interactions between rhythmic retinal processes and the central suprachiasmatic pacemaker, and propose that retinal phase shifts to light provide a critical input signal.

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

“…In nocturnal or crepuscular animals with rod-dominated retinas, rods are likely to be of predominant importance for the circadian system as mediators of dawn and dusk signals (Remé et al, 1991). Experiments with the rd mouse have shown that melatonin synthesis is not abolished by the complete loss of rod photoreceptors, while the circadian expression disappears with the loss of these photoreceptors .…”

“…Both disc shedding and autophagy follow a circadian rhythm in mammals (LaVail, 1976;Remé et al, 1985). The light history of a given animal (Penn and Williams, 1986), however, defines the amplitude of that rhythm and the overall "sensitivity" of the system to light exposure (Remé et al, 1991). Disk shedding and autophagy not only follow a circadian rhythm but may also be evoked or their amplitude modified by light exposures (Remé et al, 1998).…”

“…Rod morphology reflects ambient lighting conditions on a continuum of physiological to pathological change. While normal features are found under dim light-dark cycles, under dark-dark cycles rod length and retinal sensitivity increase, whereas under light-light cycles they decrease, with partial or total destruction (Remé et al, 1991).…”

“…Elucidation of the mechanisms by which light information is coded and transmitted to the suprachiasmatic nuclei is of obvious importance for the circadian physiology (Remé et al, 1991;Foster, 1998;von Schantz et al, 2000). Retinal physiology and light reception are modified by lighting schedules, and as a consequence of such retinal alterations, the zeitgeber input signal to the central circadian system may be affected.…”

“…Components of retinal cell biology, such as rod outer segment disk shedding, inner segment degradation, melatonin and dopamine synthesis, and electrophysiological responses, show self-sustaining circadian oscillations whose phases can be controlled by light-dark cycles (Remé et al, 1991).…”