Characterisation of light responses in the retina of mice lacking principle components of rod, cone and melanopsin phototransduction signalling pathways.
Gnat(-/-), Cnga3(-/-), Opn4(-/-) triple knockout (TKO) mice lack essential components of phototransduction signalling pathways present in rods, cones and photosensitive retinal ganglion cells (pRGCs), and are therefore expected to lack all sensitivity to light. However, a number of studies have shown that light responses persist in these mice. In this study we use multielectrode array (MEA) recordings and light-induced c-fos expression to further characterise the light responses of the TKO retina. Small, but robust electroretinogram type responses are routinely detected during MEA recordings, with properties consistent with rod driven responses. Furthermore, a distinctive pattern of light-induced c-fos expression is evident in the TKO retina, with c-fos expression largely restricted to a small subset of amacrine cells that express disabled-1 (Dab1) but lack expression of glycine transporter-1 (GlyT-1). Collectively these data are consistent with the persistence of a novel light sensing pathway in the TKO retina that originates in rod photoreceptors, potentially a rare subset of rods with distinct functional properties, and which is propagated to an atypical subtype of AII amacrine cells. Furthermore, the minimal responses observed following UV light stimulation suggest only a limited role for the non-visual opsin OPN5 in driving excitatory light responses within the mouse retina.
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Steven
S
Hughes
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Jessica
J
Rodgers
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Doron
D
Hickey
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Russell G
RG
Foster
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Stuart N
SN
Peirson
The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Sir William Dunn School of Pathology, OMPI G, South Parks Road, Oxford, OX1 3RE, UK.
Mark W
MW
Hankins
D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004596:Electroretinography; D055786:Gene Knockout Techniques; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D017299:Rod Opsins / Q000235:genetics*; D014785:Vision, Ocular; D000099210:Melanopsin
D054815:Cyclic Nucleotide-Gated Cation Channels; D020962:Heterotrimeric GTP-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D017299:Rod Opsins; D000099210:Melanopsin; C518237:Cnga3 protein, mouse