Melanopsin signalling in mammalian iris and retina

T. Xue (), M. T. H. Do, A. Riccio, Z. Jiang, J. Hsieh, H. C. Wang, S. L. Merbs, D. S. Welsbie, T. Yoshioka, P. Weissgerber, S. Stolz, V. Flockerzi, M. Freichel, M. I. Simon, D. E. Clapham and K.-W. Yau ()
Additional contact information
T. Xue: Johns Hopkins University School of Medicine
M. T. H. Do: Johns Hopkins University School of Medicine
A. Riccio: Children’s Hospital Boston, Harvard Medical School, and Howard Hughes Medical Institute
Z. Jiang: Johns Hopkins University School of Medicine
J. Hsieh: Johns Hopkins University School of Medicine
H. C. Wang: Johns Hopkins University School of Medicine
S. L. Merbs: Johns Hopkins University School of Medicine
D. S. Welsbie: Johns Hopkins University School of Medicine
T. Yoshioka: Johns Hopkins University School of Medicine
P. Weissgerber: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes
S. Stolz: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes
V. Flockerzi: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes
M. Freichel: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes
M. I. Simon: California Institute of Technology
D. E. Clapham: Children’s Hospital Boston, Harvard Medical School, and Howard Hughes Medical Institute
K.-W. Yau: Johns Hopkins University School of Medicine

Nature, 2011, vol. 479, issue 7371, 67-73

Abstract: Abstract Non-mammalian vertebrates have an intrinsically photosensitive iris and thus a local pupillary light reflex (PLR). In contrast, it is thought that the PLR in mammals generally requires neuronal circuitry connecting the eye and the brain. Here we report that an intrinsic component of the PLR is in fact widespread in nocturnal and crepuscular mammals. In mouse, this intrinsic PLR requires the visual pigment melanopsin; it also requires PLCβ4, a vertebrate homologue of the Drosophila NorpA phospholipase C which mediates rhabdomeric phototransduction. The Plcb4−/− genotype, in addition to removing the intrinsic PLR, also essentially eliminates the intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1-ipRGCs), which are by far the most photosensitive ipRGC subtype and also have the largest response to light. Ablating in mouse the expression of both TRPC6 and TRPC7, members of the TRP channel superfamily, also essentially eliminated the M1-ipRGC light response but the intrinsic PLR was not affected. Thus, melanopsin signalling exists in both iris and retina, involving a PLCβ4-mediated pathway that nonetheless diverges in the two locations.

Date: 2011
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DOI: 10.1038/nature10567

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