ABSTRACT
PURPOSE: Nuclear orphan receptors are critical for the development and long-term survival of photoreceptor cells. In the present study, the expression of the nuclear orphan receptor Esrrß--a transcriptional regulator of energy metabolism that protects rod photoreceptors from dystrophy--was tested under daily regulation in the retina and photoreceptor cells. METHODS: The daily transcript and protein amount profiles were recorded in preparations of the whole retina and microdissected photoreceptor cells using quantitative PCR (qPCR) and western blot analysis. RESULTS: Esrrß displayed a daily rhythm with elevated values at night in the whole retina and enriched photoreceptor cells. Daily regulation of Esrrß mRNA depended on light input but not on melatonin, and evoked a corresponding rhythm in the Esrrß protein. CONCLUSIONS: The data presented in this study indicate that daily regulation of Esrrß in photoreceptor cells may contribute to their adaptation to 24-h changes in metabolic demands.
Subject(s)
Circadian Rhythm/genetics , Energy Metabolism/genetics , RNA, Messenger/genetics , Receptors, Estrogen/genetics , Retina/metabolism , Retinal Rod Photoreceptor Cells/metabolism , Animals , Female , Gene Expression Regulation , Male , Mice , Mice, Inbred C57BL , Photoperiod , Primary Cell Culture , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/metabolism , Retina/cytology , Retinal Rod Photoreceptor Cells/cytology , Tissue Culture Techniques , Transcription, GeneticABSTRACT
Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor survival, such as Grk1 (G protein-coupled receptor kinase 1) and Pgc-1α (peroxisome proliferator-activated receptor γ, coactivator 1alpha). According to their daily dynamics, the genes identified could be clustered in two groups: those with peak expression during the second part of the day which are uniformly promoted to cycle by light/dark transitions and those with peak expression during the second part of the night which are predominantly driven by a clock. Since Grk1 and Pgc-1α belong in the first group, the present results support a concept in which transcriptional regulation of genes by ambient light contributes to the functional adjustment of photoreceptor cells over the 24-h period.
