May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
The Role of Cone Photoreceptors in Non–Image Forming Responses in Mice
Author Affiliations & Notes
  • G.S. Lall
    University of Manchester, Manchester, United Kingdom
  • M.W. Hankins
    Imperial College, London, United Kingdom
  • R.J. Lucas
    University of Manchester, Manchester, United Kingdom
  • Footnotes
    Commercial Relationships  G.S. Lall, None; M.W. Hankins, None; R.J. Lucas, None.
  • Footnotes
    Support  BBSRC
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3721. doi:
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      G.S. Lall, M.W. Hankins, R.J. Lucas; The Role of Cone Photoreceptors in Non–Image Forming Responses in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3721.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To evaluate the contribution of cones in non–image forming events within the mammalian visual system.

Methods: : Human red cone knock–in mice were generated by replacing the X–linked mouse green pigment gene with one encoding for the human red pigment. Wild type littermates were used as controls for all experiments. Consensual pupil light reflexes were recorded from dark–adapted (1–1.5h) mice 80–190 days old. Measurements were restricted to the middle of the light portion with animals being housed under a 12:12 light–dark cycle. Light stimuli, of 1 min duration, were generated using a xenon arc light source. Intensity and wavelength (500nm and 650nm) of light were regulated with neutral density filters and monochromatic (half bandwidths < 10nm) interference filters. Irradiance response curves were constructed from pupil light reflexes recorded in both wild type and red cone knock–in mice to 500nm and 650nm light stimuli. Phase shifting responses in wheel running activity were assesses in both red cone knock–in and wild type mice to either a 500nm (1013 photons/cm2/sec) or 650nm (1013 photons/cm2/sec) light stimulus. Light pulses were administered for 15 mins at CT 16 (4 hours after activity onset) following 7 days in constant darkness. Shifts in behavioral running rhythms were calculated by back extrapolation of a regression line fitted to 7 onsets post light stimulus. The initial 3 days following light exposure were excluded from the regression to allow for any transient effects.

Results: : Both red cone knock–in and wild type mice showed pupil constriction in response to both 500nm and 650nm light. However, while the sensitivity of these two genotypes to 500nm was indistinguishable, the red cone knock–in mice were significantly more responsive to the 650nm stimulus. Indeed, responses to all but the brightest stimulus at the two wavelengths could be predicted by correcting the relative sensitivity of cone photoreceptors in the two genotypes. Interestingly, phase shifting responses could not be elicited by even our brightest 650nm light on either genotype.

Conclusions: : Our data shows that cones dominate a pupil response to dim and intermediate light intensities. They confirm the importance of melanopsin for bright light responses but, so far, indicate that the influence of rods is negligible under these conditions. A difference in photoreceptive input between pupil and circadian responses is suggested by the lack of phase shifting elicited by 650nm light in red cone knock–in animals. Acknowledgements: we would like to thank H Cahill and J Nathans for supplying us with red cone knock–in mice.

Keywords: circadian rhythms • pupillary reflex • retina 

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