Circadian Oscillators in Retinal Ganglion Cells. Light and Dopamine Regulation and Intrinsic Photoreceptive Capacity.

GUIDO ME,

Puebla

Congreso; 3er World Congress of Chronobiology, Puebla, México, mayo 2011.; 2011

WCC-World Congress of Chronobiology

Circadian Oscillators in Retinal Ganglion Cells. Light and Dopamine Regulation and Intrinsic Photoreceptive Capacity.

 Mario E. Guido, Diego Valdez, Paula Nieto, Eduardo Garbarino-Pico, María A. Contin, Daniela Verra, Nicolás Díaz and Victoria Acosta-Rodriguez. CIQUIBIC-Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba-CONICET, 5000 Córdoba, Argentina Email: mguido@fcq.unc.edu.ar,

Retinal clocks induce changes in the visual system as a function of the time of day in anticipation of the illumination variations occurring at dawn and dusk. Retinal ganglion cells (RGCs) send visual and circadian information to the brain regarding the environmental illumination and a subset of cells was shown to be intrinsically photosensitive. In the chicken retina, RGCs contain autonomous circadian oscillators that synthesize melatonin with higher levels during the subjective day in constant darkness (DD), light (LL) or light phase of a 12:12 h LD cycle in antiphase to the nocturnal rhythm observed in photoreceptor cells (PRCs). RGCs also display the expression and activity of arylalkylamine N-acetyltransferase (AA-NAT), a key enzyme in melatonin biosynthesis, with the highest levels during the subjective day. Remarkably, in LL, the rhythm in AA-NAT mRNA expression is lost in PRCs but still observed in RGCs. To further investigate light responses, we assessed the presence of photopigments in RGCs, their intrinsic photosensitivity and the effect of light and dopamine (DA) on AA-NAT activity; in this context, DA may mimic the effect of light. When we examined the expression of clock genes and AA-NAT in the rat RGC line RGC-5, we found that dividing cells express the RGC marker Thy-1 together with Per1, Clock and Bmal1 and AA-NAT. RGC-5 also express a number of photopigments (Opn3, Opn5 and RGR) while chicken RGCs express melanopsin (Opn4). Moreover, both chicken RGCs and RGC-5 cells respond to light stimulation causing significant changes in intracellular Ca2+ mobilization. By contrast, a light pulse of 30-60 min during the subjective day (CT 3) or subjective night (CT 17.5) caused a significant decrease in AA-NAT activity of PRCs while  has no effect on RGC enzyme activity. DA treatment in the absence of light significantly inhibited AA-NAT activity in PRCs but not in RGCs. Overall the results suggest that chicken RGCs and the mammalian RGC-5 expressing non-visual photopigments may act as non-visual photoreceptors while in the chicken retina, circadian rhythms observed in PRCs and RGCs are differentially regulated by light, DA and the circadian clock. The convergence of oscillatory and photoreceptive capacities in retinal cells and particularly in vertebrate RGCs could deeply impact on the functioning of the circadian system to temporally regulate physiology and behavior.

 

Supported by ANPCyT-FONCyT,(PICT 04 967/PICT06 898), CONICET, SeCyT-UNC, and MinCyT-Cba.