Article | Published:

Characterization of an ocular photopigment capable of driving pupillary constriction in mice

Nature Neuroscience volume 4, pages 621626 (2001) | Download Citation

Subjects

Abstract

This work demonstrates that transgenic mice lacking both rod and cone photoreceptors (rd/rd cl) retain a pupillary light reflex (PLR) that does not rely on local iris photoreceptors. These data, combined with previous reports that rodless and coneless mice show circadian and pineal responses to light, suggest that multiple non-image-forming light responses use non-rod, non-cone ocular photoreceptors in mice. An action spectrum for the PLR in rd/rd cl mice demonstrates that over the range 420–625 nm, this response is driven by a single opsin/vitamin A-based photopigment with peak sensitivity around 479 nm (opsin photopigment/OP479). These data represent the first functional characterization of a non-rod, non-cone photoreceptive system in the mammalian CNS.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Circadian photoreception in the retinally degenerate mouse (rd/rd). J. Comp. Physiol. 169, 39–50 (1991).

  2. 2.

    & Rapid light-induced decrease in pineal serotonin N-acetyltransferase activity. Science 177, 532–533 (1972).

  3. 3.

    et al. Bright light effects on body temperature, alertness, EEG and behavior. Physiol. Behav. 50, 583–588 (1991).

  4. 4.

    , & Dynamics of EEG slow-wave activity and core body temperature in human sleep after exposure to bright light. Sleep 15, 337–323 (1992).

  5. 5.

    , , & Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness. Behav. Brain Res. 115, 75–83 (2000).

  6. 6.

    & Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus). J. Physiol. (Lond.) 439, 115–145 (1991).

  7. 7.

    , & Retinal projections in mice with inherited retinal degeneration: implications for circadian photoentrainment. J. Comp. Neurol. 395, 417–439 (1998).

  8. 8.

    Shedding light on the biological clock. Neuron 20, 829–832 (1998).

  9. 9.

    Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suprachiasmatic nucleus and the intergeniculate leaflet of the thalamus. Neurosci. Lett. 55, 211–217 (1985).

  10. 10.

    et al. Photoreceptors regulating circadian behavior: a mouse model. J. Biol. Rhythms 8, S17–S23 (1993).

  11. 11.

    & The influence of different light intensities on pineal melatonin content in the retinal degenerate C3H mouse and the normal CBA mouse. Neurosci. Lett. 108, 267–272 (1990).

  12. 12.

    et al. Visual and circadian responses to light in aged retinally degenerate mice. Vision Res. 34, 1799–1806 (1994).

  13. 13.

    et al. Suppression of melatonin secretion in some blind patients by exposure to bright light. N. Engl. J. Med. 332, 6–11 (1995).

  14. 14.

    et al. Relationship between melatonin rhythms and visual loss in the blind. J. Clin. Endocrinol. Metab. 82, 3763–3770 (1997).

  15. 15.

    Iris movements in blind mice. Am. J. Physiol. 81, 107–112 (1927).

  16. 16.

    & Retinal sensitivity measured by the pupillary light reflex in RCS and albino rats. Vision Res. 22, 1163–1171 (1982).

  17. 17.

    et al. The intensity of the pupillary light reflex does not correlate with the number of retinal photoreceptor cells. Exp. Neurol. 133, 43–49 (1995).

  18. 18.

    & Spectral sensitivity of photoreceptors mediating phase-shifts of circadian rhythms in retinally degenerate CBA/J (rd/rd) and normal CBA/N (+/+) mice. J. Comp. Physiol. 178, 797–802 (1996).

  19. 19.

    et al. Changes in the pupillary light reflex of pigmented royal college of surgeons rats with age. Exp. Eye Res. 66, 719–730 (1998).

  20. 20.

    , & Thresholds for masking responses to light in three strains of retinally degenerate mice. J. Comp. Physiol. 184, 423–428 (1999).

  21. 21.

    et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284, 502–504 (1999).

  22. 22.

    et al. Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 284, 505–507 (1999).

  23. 23.

    & Absence of extra-ocular photoreception in diurnal and nocturnal rodents exposed to direct sunlight. Comp. Biochem. Physiol. 69A, 145–148 (1981).

  24. 24.

    , & Recent developments in circadian photoreception: more than meets the eye. Invest. Ophthalmol. Vis. Sci. 41, 1605–1607 (2000).

  25. 25.

    , & Retinal receptors in rodents maximally sensitive to ultraviolet light. Nature 353, 655–656 (1991).

  26. 26.

    ed. The Ecology of Vision (Oxford Univ. Press, Oxford, 1979).

  27. 27.

    , & eds., The Photobiology of Vision (Academic, New York, 1977).

  28. 28.

    & The spectral sensitivity of the consensual light reflex. J. Physiol. 164, 478–507 (1962).

  29. 29.

    & The effect of bleaching and backgrounds on pupil size. Vision Res. 12, 943–951 (1972).

  30. 30.

    & Adaptation of the pupil light reflex. Vision Res. 12, 953–967 (1972).

  31. 31.

    , , & Improvement of the pupillary light reflex of Royal College of Surgeons rats following RPE cell grafts. Exp. Neurol. 140, 100–104 (1996).

  32. 32.

    et al. Extent and duration of recovered pupillary light reflex following retinal ganglion cell axon regeneration through peripheral nerve grafts directed to the pretectum in adult rats. Exp. Neurol. 154, 560–572 (1998).

  33. 33.

    & The anatomical substrates subserving the pupillary light reflex in rats: origin of the consensual pupillary response. Neuroscience 62, 481–496 (1994).

  34. 34.

    & Photoactivation of pupillary constriction in the isolated in vitro iris of a mammal (Mesocricetus auratus). Comp. Biochem. Physiol. A Mol. Integr. Physiol. 50, 407–413 (1975).

  35. 35.

    , , & Pupillary constriction in response to light in rodents, which does not depend on central neural pathways. J. Neurol. Sci. 113, 70–79 (1992).

  36. 36.

    , , & Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse. Neuropharmacology 36, 135–143 (1997).

  37. 37.

    The visual pigments of some common laboratory animals. Nature 184, 1727–1728 (1959).

  38. 38.

    , & Mechanisms of spectral tuning in the mouse green cone pigment. Proc. Natl. Acad. Sci. USA 94, 8860–8865 (1997).

  39. 39.

    et al. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347, 677–680 (1990).

  40. 40.

    , & Differential effect of the rd mutation on rods and cones in the mouse retina. Invest. Ophthalmol. Vis. Sci. 17, 489–498 (1978).

  41. 41.

    et al. A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina. Neuron 21, 481–493 (1998).

  42. 42.

    , ed. Light Detectors, Photoreceptors, and Imaging Systems in Nature (Oxford Univ. Press, New York, 1995).

  43. 43.

    & A new template for rhodopsin (vitamin A1 based) visual pigments. Vision Res. 31, 619–630 (1991).

  44. 44.

    et al. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc. Natl. Acad. Sci. USA 97, 14607–14702 (2000).

  45. 45.

    et al. A novel human opsin in the inner retina. J. Neurosci. 20, 600–605 (2000).

  46. 46.

    , & Rhodopsin-like sensitivity of extra-retinal photoreceptors mediating the photoperiodic response in quail. Nature 313, 50–52 (1985).

  47. 47.

    Kundt's rule: the spectral absorbance of visual pigments in situ and in solution. Vision Res. 12, 529–548 (1972).

  48. 48.

    & Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Res. 694, 183–190 (1995).

Download references

Acknowledgements

This work was supported by the BBSRC. The authors thank N. Mrosovsky for comments on an earlier version of this manuscript and S. Thompson and M. Semo for technical assistance.

Author information

Affiliations

  1. Department of Integrative & Molecular Neuroscience, Division of Neuroscience & Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK

    • Robert J. Lucas
    •  & Russell G. Foster
  2. Applied Vision Research Centre, Department of Optometry & Visual Science, City University, Northampton Sq., London EC1V 0HB, UK

    • Ronald H. Douglas

Authors

  1. Search for Robert J. Lucas in:

  2. Search for Ronald H. Douglas in:

  3. Search for Russell G. Foster in:

Corresponding author

Correspondence to Robert J. Lucas.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/88443