Mechanisms of photoperception and circadian control in an animal model of blindness
Mario E. Guido
Department of Biological Chemistry-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Córdoba, ARGENTINA
In birds, pacemakers located in the central nervous system comprise the hypothalamic suprachiasmatic nucleus, the retina and the pineal gland. The retina, the pineal gland and the extraretinal photoreceptors are responsible for photoreception of the environmental lighting conditions that synchronize central oscillators. The retina is rhythmic itself, containing an autonomous clock mechanism that generates daily rhythms in molecular and physiological parameters. It is not clear yet whether the different retinal cells contain functional circadian clocks. In the chicken retina, it has been shown the presence of circadian oscillators in photoreceptors (PRCs), retinal ganglion cells (RGCs) and inner nuclear layer cells (INL). The GUCY1* chicken carries an autosomal recessive mutation that results in the degeneration of their photoreceptors cones and rods, causing blindness at hatch similar to the Leber´s congenital amaurosis (LCA) in humans. The GUCY1* chicken constitutes an excellent model to study light synchronization in the absence of functional classical photoreceptors (cones and rods). To better characterize these animals, we first assessed the electric responses of the retina to light pulses of high intensities by electroretinogram (ERG) recordings, and a totally null responsiveness was obtained denoting a typical clinically blind subject. However, these animals were able to display detectable pupillary responses to light of different wavelengths with a faster response to light pulses of approximately 480 nm and a circadian profile showing higher responses at midday. The GUCY1* RGCs exhibit detectable levels of enzyme activity for serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyl transferase (HIOMT), two key enzymes of the biosynthesis of melatonin, with differential patterns of daily activity. When we assessed the feeding activity, we observed that these animals exhibit circadian rhythms of food intake that are entrained to different 12:12 h LD cycles (white or blue light of ~700-1000 lux). In LL, the GUCY1* chickens became arrhythmic except when they have their pineal gland occluded; in this condition, they free run with a period of about 24.6 h. Taken all the observations together, we may infer that in birds, the photoperception is occurring even in the absence of functional PRCs; however, a complex mechanism involving both the RGCs in the inner retina and the pineal gland is acting to regulate the temporal organization of physiology.
