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Effect of Vitamin A Depletion on Nonvisual Phototransduction Pathways in Cryptochromeless Mice
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
Institute of Cancer Research, Columbia University College of Physicians and Surgeons, New York, New York
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260aziz_sancar{at}med.unc.edu 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.
Key Words: circadian photoreception • c-fos induction • retina • opsin • vitamin A • retinolbinding protein
Journal of Biological Rhythms, Vol. 19, No. 6,
504-517 (2004) This article has been cited by other articles:
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