Retina-specific glucocorticoid receptor deletion disrupts rhythmic gene expression in the mouse retina under constant dark conditions.

The ocular circadian clock has been thought to be regulated primarily by environmental light. In many peripheral tissues, however, circadian clocks are influenced by temporal information conveyed by adrenal glucocorticoids, while glucocorticoid-dependent regulation of the eye clock, a light-receptive organ, has remained unclear. To investigate this mechanism, we generated retina-specific Nr3c1 (glucocorticoid receptor; GR) knockout mice by crossing Chx10-Cre mice, in which Cre-recombinase is driven by the Chx10 promoter expressed in the developing optic cup, with Nr3c1 flox/flox mice. Using these mice, we performed time-course tissue collection under constant dark conditions followed by time-series RNA-seq analysis. The analysis showed that many rhythmic genes detected in control retina were lost in retina-specific Nr3c1-deficient mice, suggesting that glucocorticoid signaling contributes to rhythmic retinal gene expression.