Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

The mechanisms that synchronize the biorhythms of the mammalian retina with the light/dark cycle are independent of those synchronizing the rhythms in the central pacemaker, the suprachiasmatic nucleus. The identity of the photoreceptor(s) responsible for the light entrainment of the retina of mammals is still a matter of debate, and recent studies have reported contradictory results in this respect. Here, we suggest that cryptochromes (CRY), in particular CRY 2, are involved in that light entrainment. CRY are highly conserved proteins that are a key component of the cellular circadian clock machinery. In plants and insects, they are responsible for the light entrainment of these biorhythms, mediated by the light response of their flavin cofactor (FAD). In mammals, however, no light-dependent role is currently assumed for CRY in light-exposed tissues, including the retina. It has been reported that FAD influences the function of mammalian CRY 2 and that human CRY 2 responds to light in Drosophila, suggesting that mammalian CRY 2 keeps the ability to respond to light. Here, we hypothesize that CRY 2 plays a role in the light entrainment of retinal biorhythms, at least in diurnal mammals. Indeed, published data shows that the light intensity dependence and the wavelength sensitivity commonly reported for that light entrainment fits the light sensitivity and absorption spectrum of light-responsive CRY. We propose experiments to test our hypothesis and to further explore the still-pending question of the function of CRY 2 in the mammalian retina.