Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina

PURPOSE. The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D-4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1 alpha, Ror beta) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D-4 receptors. METHODS. This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D-4 receptors. RESULTS. The data obtained determined Pgc-1 alpha and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling, respectively. CONCLUSIONS. The results suggest that Pgc-1 alpha and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells.