Effect of vitamin A depletion on nonvisual phototransduction pathways in cryptochromeless mice

Mice exhibit multiple nonvisual responses to light, including 1) photoentrainment of circadian rhythm; 2) masking, which refers to the acute effect of light on behavior, either negative (activity suppressing) or positive (activity inducing); and 3) pupillary constriction. In mammals, the eye is the sole photosensory organ for these responses, and it contains only 2 known classes of pigments: opsins and cryptochromes. No individual opsin or cryptochrome gene is essential for circadian photoreception, gene photoinduction, or masking. Previously, the authors found that mice lacking retinol-binding protein, in which dietary depletion of ocular retinaldehyde can be achieved, had normal light signaling to the SCN, as determined by per gene photoinduction. In the present study, the authors analyzed phototransduction to the SCN in vitamin A-replete and vitamin A-depleted rbp-/- and rbp-/- cryl-/-cry2-/- mice using molecular and behavioral end points. They found that vitamin A-depleted rbp-/- mice exhibit either normal photoentrainment or become diurnal. In contrast, while vitamin A-replete rbp-/- cryl-/- cry2-/- mice are light responsive (with reduced sensitivity), vitamin A-depleted rbp-/- cry1-/- cry2-/- mice, which presumably lack functional opsins and cryptochromes, lose most behavioral and molecular responses to light. These data demonstrate that both cryptochromes and opsins regulate nonvisual photoresponses.