The retinal clock in mammals: role in health and disease

Abstract

The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN). This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental processes, the coherence from cell to tissue is critical for circadian functions, and disruption of retinal clock organization or its response to light can potentially have a major impact on retinal pathophysiology and vision.