Skip to main content
×
Home
    • Aa
    • Aa

Residual photosensitivity in mice lacking both rod opsin and cone photoreceptor cyclic nucleotide gated channel 3 α subunit

  • ALUN R. BARNARD (a1) (a2), JOANNE M. APPLEFORD (a1), SUMATHI SEKARAN (a1), KRISHNA CHINTHAPALLI (a1), AARON JENKINS (a1), MATHEAS SEELIGER (a3), MARTIN BIEL (a4), PETER HUMPHRIES (a5), RON H. DOUGLAS (a6), ANDREAS WENZEL (a7), RUSSELL G. FOSTER (a1), MARK W. HANKINS (a1) and ROBERT J. LUCAS (a1) (a2)...
Abstract

The mammalian retina contains three classes of photoreceptor. In addition to the rods and cones, a subset of retinal ganglion cells that express the putative sensory photopigment melanopsin are intrinsically photosensitive. Functional and anatomical studies suggest that these inner retinal photoreceptors provide light information for a number of non-image-forming light responses including photoentrainment of the circadian clock and the pupil light reflex. Here, we employ a newly developed mouse model bearing lesions of both rod and cone phototransduction cascades (Rho−/−Cnga3−/−) to further examine the function of these non-rod non-cone photoreceptors. Calcium imaging confirms the presence of inner retinal photoreceptors in Rho−/−Cnga3−/− mice. Moreover, these animals retain a pupil light reflex, photoentrainment, and light induction of the immediate early gene c-fos in the suprachiasmatic nuclei, consistent with previous findings that pupillary and circadian responses can employ inner retinal photoreceptors. Rho−/−Cnga3−/− mice also show a light-dependent increase in the number of FOS-positive cells in both the ganglion cell and (particularly) inner nuclear layers of the retina. The average number of cells affected is several times greater than the number of melanopsin-positive cells in the mouse retina, suggesting functional intercellular connections from these inner retinal photoreceptors within the retina. Finally, however, while we show that wild types exhibit an increase in heart rate upon light exposure, this response is absent in Rho−/−Cnga3−/− mice. Thus, it seems that non-rod non-cone photoreceptors can drive many, but not all, non-image-forming light responses.

Copyright
Corresponding author
Address correspondence and reprint requests to: Robert J. Lucas, Faculty of Life Sciences, University of Manchester, Oxford Rd., Manchester M13 9PT, UK. E-mail: r.j.lucas@ic.ac.uk
References
Hide All

REFERENCES

Albrecht, U. & Foster, R.G. (2002). Placing ocular mutants into a functional context: A chronobiological approach. Methods 28, 465477.
Belenky, M.A., Smeraski, C.A., Provencio, I., Sollars, P.J., & Pickard, G.E. (2003). Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. Journal of Comparative Neurology 460, 380393.
Benca, R.M., Gilliland, M.A., & Obermeyer, W.H. (1998). Effects of lighting conditions on sleep and wakefulness in albino lewis and pigmented brown norway rats. Sleep 21, 451460.
Berson, D., Dunn, F., & Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 10701073.
Biel, M., Seeliger, M., Pfeifer, A., Kohler, K., Gerstner, A., Ludwig, A., Jaissle, G., Fauser, S., Zrenner, E., & Hofmann, F. (1999). Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel cng3. Proceedings of the National Academy Sciences of the U.S.A. 96, 75537557.
Bowes, C., Li, T., Danciger, M., Baxter, L.C., Applebury, M.L., & Farber, D.B. (1990). Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347, 677680.
Cajochen, C., Zeitzer, J.M., Czeisler, C.A., & Dijk, D.-J. (2000). Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness. Behavioral Brain Research 115, 7583.
Carter-Dawson, L.D., Lavail, M.M., & Sidman, R.L. (1978). Differential effect of the rd mutation on rods and cones in the mouse retina. Investigative Ophthalmology and Visual Sciences 17, 489498.
Czeisler, C.A., Shanahan, T.L., Klerman, E.B., Martens, H., Brotman, D.J., Emens, J.S., Klein, T., & Rizzo, J.F. (1995). Suppression of melatonin secretion in some blind patients by exposure to bright light. New England Journal of Medicine 332, 611.
Ebihara, S. & Tsuji, K. (1980). Entrainment of the circadian activity rhythm to the light cycle: Effective light intensity for a zeitgeber in the retinal degenerate c3h mouse and the normal c57bl mouse. Physiology & Behavior 24, 523527.
Foster, R.G., Provencio, I., Hudson, D., Fiske, S., De Grip, W., & Menaker, M. (1991). Circadian photoreception in the retinally degenerate mouse (rd/rd). Journal of Comparative Physiology (A) 169, 3950.
Freedman, M.S., Lucas, R.J., Soni, B., von Schantz, M., Munoz, M., David-Gray, Z., & Foster, R.G. (1999). Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284, 502504.
Gooley, J.J., Lu, J., Chou, T.C., Scammell, T.E., & Saper, C.B. (2001). Melanopsin in cells of origin of the retinohypothalamic tract. Nature Neuroscience 4, 1165.
Gooley, J.J., Lu, J., Fischer, D., & Saper, C.B. (2003). A broad role for melanopsin in nonvisual photoreception. Journal of Neuroscience 23, 70937106.
Hankins, M.W. & Lucas, R.J. (2002). The primary visual pathway in humans is regulated according to long-term light exposure through the action of a nonclassical photopigment. Current Biology 12, 191198.
Hannibal, J., Hindersson, P., Knudsen, S.M., Georg, B., & Fahrenkrug, J. (2002). The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract. Journal Neuroscience 22, RC191.
Hattar, S., Liao, H.-W., Takao, M., Berson, D., & Yau, K.-W. (2002). Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity. Science 295, 10651070.
Hattar, S., Lucas, R.J., Mrosovsky, N., Thompson, S., Douglas, R.H., Hankins, M.W., Lem, J., Biel, M., Hofmann, F., Foster, R.G., & Yau, K.W. (2003). Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424, 7581.
Haverkamp, S., Claes, E., Humphries, P., Biel, M., & Seeliger, M. (2003). Morphological alterations in the retina of cng3−/− / rho−/− double mutant mice. Investigative Ophthalmology Visual Science 44, Abstract 2830.
Huerta, J.J., Llamosas, M.M., Cernuda-Cernuda, R., & Garcia-Fernandez, J.M. (1997). Fos expression in the retina of rd/rd mice during the light/dark cycle. Neuroscience Letters 232, 143146.
Humphries, M., Rancourt, D., Farrar, G., Kenna, P., Hazel, M., Bush, R., Sieving, P., Sheils, D., Mcnally, N., Creighton, P., Erven, A., Boros, A., Gulya, K., Capecchi, M., & Humphries, P.H. (1997). Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nature Genetics 15, 216219.
Klerman, E., Shanahan, T., Brotman, D., Rimmer, D., Emens, J., Rizzo, J., & Czeisler, C. (2002). Photic resetting of the human circadian pacemaker in the absence of conscious vision. Journal of Biological Rhythms 17, 548555.
Lockley, S.W., Skene, D.J., Arendt, J., Tabandeh, H., Bird, J.C., & Defrance, R. (1997). Relationship between melatonin rhythms and visual loss in the blind. Journal of Clinical Endocrinology and Metabolism 82, 37633770.
Lucas, R., Douglas, R., & Foster, R. (2001). Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nature Neuroscience 4, 621626.
Lucas, R.J., Freedman, M.S., Munoz, M., Garcia-Fernandez, J.M., & Foster, R.G. (1999). Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 284, 505507.
Lucas, R.J., Hattar, S., Takao, M., Berson, D.M., Foster, R.G., & Yau, K.W. (2003). Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299, 245247.
Lupi, D., Cooper, H., Froehlich, A., Standford, L., Mccall, M., & Foster, R. (1999). Transgenic ablation of rod photoreceptors alters the circadian phenotype of mice. Neuroscience 89, 363374.
Morin, L., Blanchard, J., & Provencio, I. (2003). Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet and visual midbrain: Bifurcation and melanopsin immunoreactivity. Journal of Comparative Neurology 465, 401416.
Mrosovsky, N. (1994). In praise of masking: Behavioural responses of retinally degenerate mice to dim light. Chronobiology International 11, 343348.
Mrosovsky, N. & Salmon, P.A. (2002). Learned arbitrary responses to light in mice without rods or cones. Naturwissenschaften 89, 525527.
Mrosovsky, N., Foster, R.G., & Salmon, P.A. (1999). Thresholds for masking responses to light in three strains of retinally degenerate mice. Journal of Comparative Physiology A 184, 423428.
Mrosovsky, N., Lucas, R., & Foster, R. (2001). Persistence of masking responses to light in mice lacking rods and cones. Journal of Biological Rhythms 16, 585587.
Mrosovsky, N. & Hattar, S. (2003). Impaired masking responses to light in melanopsin-knockout mice. Chronobiology International 20, 989999.
Mutoh, T., Shibata, S., Korf, H.W., & Okamura, H. (2003). Melatonin modulates the light-induced sympathoexcitation and vagal suppression with participation of the suprachiasmatic nucleus in mice. Journal of Physiology 547, 317332.
Panda, S., Sato, T.K., Castrucci, A.M., Rollag, M.D., Degrip, W.J., Hogenesch, J.B., Provencio, I., & Kay, S.A. (2002). Melanopsin (opn4) requirement for normal light-induced circadian phase shifting. Science 301, 22132216.
Panda, S., Provencio, I., Tu, D.C., Pires, S.S., Rollag, M.D., Castrucci, A.M., Pletcher, M.T., Sato, T.K., Wiltshire, T., Andahazy, M., Kay, S.A., Van Gelder, R.N., & Hogenesch, J.B. (2003). Melanopsin is required for non-image-forming photic responses in blind mice. Science 301, 525527.
Provencio, I. & Foster, R. (1995). Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Research 694, 183190.
Provencio, I., Rollag, M., & Castrucci, A. (2002). Photoreceptive net in the mammalian retina. Nature 415, 493.
Rieux, C., Carney, R., Lupi, D., Dkhissi-Benyahya, O., Jansen, K., Chounlamountri, N., Foster, R.G., & Cooper, H.M. (2002). Analysis of immunohistochemical label of fos protein in the suprachiasmatic nucleus: Comparison of different methods of quantification. Journal of Biological Rhythms 17, 121136.
Ruby, N.F., Brennan, T.J., Xie, X., Cao, V., Franken, P., Heller, H.C., & O'hara, B.F. (2002). Role of melanopsin in circadian responses to light. Science 298, 22112213.
Scheer, F.A., Van Doornen, L.J., & Buijs, R.M. (1999). Light and diurnal cycle affect human heart rate: Possible role for the circadian pacemaker. Journal of Biological Rhythms 14, 202212.
Scheer, F.A., Ter Horst, G.J., Van Der Vliet, J., & Buijs, R.M. (2001). Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats. American Journal of Physiology: Heart and Circulatory Physiology 280, H1391H1399.
Seeliger, M.W., Grimm, C., Stahlberg, F., Friedburg, C., Jaissle, G., Zrenner, E., Guo, H., Reme, C.E., Humphries, P., Hofmann, F., Biel, M., Fariss, R.N., Redmond, T.M., & Wenzel, A. (2001). New views on RPE65 deficiency: The rod system is the source of vision in a mouse model of Leber congenital amaurosis. Nature Genetics 29, 7074.
Sekaran, S., Foster, R.G., Lucas, R.J., & Hankins, M.W. (2003). Calcium imaging reveals a network of intrinsically light sensitive inner retinal neurones. Current Biology 13, 12901298.
Semo, M., Lupi, D., Peirson, S.N., Butler, J.N., & Foster, R.G. (2003). Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice. European Journal of Neuroscience 18, 30073017.
Soucy, E., Wang, Y., Nirenberg, S., Nathans, J., & Meister, M. (1998). A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina. Neuron 21, 481493.
Strettoi, E., Porciatti, V., Falsini, B., Pignatelli, V., & Rossi, C. (2002). Morphological and functional abnormalities in the inner retina of the rd/rd mouse. Journal of Neuroscience 22, 54925504.
Trejo, L.J. & Cicerone, C.M. (1982). Retinal sensitivity measured by the pupillary light reflex in rcs and albino rats. Vision Research 22, 11631171.
Warren, E.J., Allen, C.N., Brown, R.L., & Robinson, D.W. (2003). Intrinsic light responses of retinal ganglion cells projecting to the circadian system. European Journal Neuroscience 17, 17271735.
Yoshimura, T. & Ebihara, S. (1996). Spectral sensitivity of photoreceptors mediating phase-shifts of circadian rhythms in retinally degenerate cba/j (rd/rd) and normal cba/n (+/+) mice. Journal of Comparative Physiology (A) 178, 797802.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 6
Total number of PDF views: 42 *
Loading metrics...

Abstract views

Total abstract views: 284 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th October 2017. This data will be updated every 24 hours.