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Effect of vitamin A depletion on nonvisual phototransduction pathways in cryptochromeless mice
Carol L Thompson1, Christopher P Selby, Russell N Van Gelder
1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Abstract:
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-/-cry1-/-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-/-cry1-/-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.
Insights
Both opsins and cryptochromes are essential for nonvisual light responses in mice, regulating circadian rhythms and behavior. These findings highlight the complex roles of these photoreceptors in mammalian light perception.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Mice display various nonvisual light responses, including circadian photoentrainment, behavioral masking, and pupillary constriction.
- These responses are mediated by the eye using opsins and cryptochromes, but no single gene is essential for all light signaling.
- Previous work showed normal light signaling to the SCN in mice lacking retinol-binding protein (rbp-/-) with depleted retinaldehyde.
Purpose of the Study:
- To investigate the roles of opsins and cryptochromes in nonvisual phototransduction to the suprachiasmatic nucleus (SCN).
- To analyze light responses in vitamin A-replete and depleted mice with genetic modifications affecting opsin and cryptochrome function.
Main Methods:
- Utilized molecular and behavioral endpoints in rbp-/- and rbp-/-cry1-/-cry2-/- mice under varying vitamin A conditions.
- Assessed photoentrainment, circadian rhythm regulation, and gene photoinduction (per gene) as indicators of light signaling.
Main Results:
- Vitamin A-depleted rbp-/- mice showed normal photoentrainment or became diurnal.
- Vitamin A-replete rbp-/-cry1-/-cry2-/- mice remained light responsive, albeit with reduced sensitivity.
- Vitamin A-depleted rbp-/-cry1-/-cry2-/- mice, lacking functional opsins and cryptochromes, lost most behavioral and molecular light responses.
Conclusions:
- Both opsins and cryptochromes are crucial regulators of nonvisual photoresponses in mice.
- These photoreceptors play distinct yet cooperative roles in mediating light's effects on circadian rhythms and behavior.
- The study elucidates the necessity of both opsin and cryptochromes for comprehensive light perception in mammals.
