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Profound defects in pupillary responses to light in TRPM-channel null mice: a role for TRPM channels in non-image-forming photoreception.

Abstract:
TRPM1 is a spontaneously active non-selective cation channel that has recently been shown to play an important role in the depolarizing light responses of ON bipolar cells. Consistent with this role, mutations in the TRPM1 gene have been identified as a principal cause of congenital stationary night blindness. However, previous microarray studies have shown that Trpm1 and Trpm3 are acutely regulated by light in the eyes of mice lacking rods and cones (rd/rd cl), a finding consistent with a role in non-image-forming photoreception. In this study we show that pupillary light responses are significantly attenuated in both Trpm1(-/-) and Trpm3(-/-) animals. Trpm1(-/-) mice exhibit a profound deficit in the pupillary response that is far in excess of that observed in mice lacking rods and cones (rd/rd cl) or melanopsin, and cannot be explained by defects in bipolar cell function alone. Immunolocalization studies suggest that TRPM1 is expressed in ON bipolar cells and also a subset of cells in the ganglion cell layer, including melanopsin-expressing photosensitive retinal ganglion cells (pRGCs). We conclude that, in addition to its role in bipolar cell signalling, TRPM1 is involved in non-image-forming responses to light and may perform a functional role within pRGCs. By contrast, TRPM3(-/-) mice display a more subtle pupillary phenotype with attenuated responses under bright light and dim light conditions. Expression of TRPM3 is detected in Muller cells and the ciliary body but is absent from pRGCs, and thus our data support an indirect role for TRPM3 in pupillary light responses.
Publication status:
Published

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Publisher copy:
10.1111/j.1460-9568.2011.07944.x

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author


Journal:
European journal of neuroscience More from this journal
Volume:
35
Issue:
1
Pages:
34-43
Publication date:
2012-01-01
DOI:
EISSN:
1460-9568
ISSN:
0953-816X


Language:
English
Keywords:
Pubs id:
pubs:222363
UUID:
uuid:fb14a6df-5c60-4180-a510-7d499cf1a2db
Local pid:
pubs:222363
Source identifiers:
222363
Deposit date:
2012-12-19

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