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Science 8 February 2002:
Vol. 295. no. 5557, pp. 1065 - 1070
DOI: 10.1126/science.1069609
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Reports

Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity

S. Hattar,12* H.-W. Liao,2* M. Takao,4 D. M. Berson,4 K.-W. Yau123dagger

The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, beta -galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non-image-forming visual functions.

1 Howard Hughes Medical Institute and Departments of
2 Neuroscience and
3 Ophthalmology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
4 Department of Neuroscience, Brown University, Providence, RI 02912, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: kwyau{at}mail.jhmi.edu

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G. Glickman, J. P. Hanifin, M. D. Rollag, J. Wang, H. Cooper, and G. C. Brainard (2003)
J Biol Rhythms 18, 71-79
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Reduced Pupillary Light Responses in Mice Lacking Cryptochromes.
R. N. Van Gelder, R. Wee, J. A. Lee, and D. C. Tu (2003)
Science 299, 222
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Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice.
R. J. Lucas, S. Hattar, M. Takao, D. M. Berson, R. G. Foster, and K.-W. Yau (2003)
Science 299, 245-247
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Role of Melanopsin in Circadian Responses to Light.
N. F. Ruby, T. J. Brennan, X. Xie, V. Cao, P. Franken, H. C. Heller, and B. F. O'Hara (2002)
Science 298, 2211-2213
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Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting.
S. Panda, T. K. Sato, A. M. Castrucci, M. D. Rollag, W. J. DeGrip, J. B. Hogenesch, I. Provencio, and S. A. Kay (2002)
Science 298, 2213-2216
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Circadian Photoreception in Humans and Mice.
I. H. Kavakli and A. Sancar (2002)
Mol. Interv. 2, 484-492
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Mapping Quantitative Trait Loci Affecting Circadian Photosensitivity in Retinally Degenerate Mice.
T. Yoshimura, Y. Yokota, A. Ishikawa, S. Yasuo, N. Hayashi, T. Suzuki, N. Okabayashi, T. Namikawa, and S. Ebihara (2002)
J Biol Rhythms 17, 512-519
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