Visual Neuroscience



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


ALUN R.  BARNARD  a1 a7 , JOANNE M.  APPLEFORD  a1 , SUMATHI  SEKARAN  a1 , KRISHNA  CHINTHAPALLI  a1 , AARON  JENKINS  a1 , MATHEAS  SEELIGER  a2 , MARTIN  BIEL  a3 , PETER  HUMPHRIES  a4 , RON H.  DOUGLAS  a5 , ANDREAS  WENZEL  a6 , RUSSELL G.  FOSTER  a1 , MARK W.  HANKINS  a1 and ROBERT J.  LUCAS  a1 a7 c1
a1 Department of Integrative and Molecular Neuroscience, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, London, UK
a2 Retinal Electrodiagnostics Research Group, University Eye Hospital Tübingen, Department of Pathophysiology of Vision and Neuroophthalmology, Tübingen, Germany
a3 Lehrstuhl Pharmakologie für Naturwissenshcaften, Zentrum für Pharmaforschung, Ludwig-Maximilians Universität München, München, Germany
a4 Department of Genetics, Trinity College Dublin, Republic of Ireland
a5 Department of Optometry and Visual Science, City University, Northampton Square, London, UK
a6 Laboratory for Retinal Cell Biology, ONO-EM, H-Lab-13, Zürich, Switzerland
a7 Faculty of Life Sciences, University of Manchester, Manchester, UK

Article author query
barnard ar   [Google Scholar] 
appleford jm   [Google Scholar] 
sekaran s   [Google Scholar] 
chinthapalli k   [Google Scholar] 
jenkins a   [Google Scholar] 
seeliger m   [Google Scholar] 
biel m   [Google Scholar] 
humphries p   [Google Scholar] 
douglas rh   [Google Scholar] 
wenzel a   [Google Scholar] 
foster rg   [Google Scholar] 
hankins mw   [Google Scholar] 
lucas rj   [Google Scholar] 
 

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.

(Received October 20 2003)
(Accepted May 27 2004)


Key Words: Melanopsin; Circadian entrainment; Retinal degeneration; Heart rate; Light.

Correspondence:
c1 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