title: Rod- and cone-driven responses in mice expressing human L-cone pigment.
abstract: The mouse is commonly used for studying retinal processing, primarily because it is amenable to genetic manipulation. To accurately study photoreceptor driven signals in the healthy and diseased retina, it is of great importance to isolate the responses of single photoreceptor types. This is not easily achieved in mice because of the strong overlap of rod and M-cone absorption spectra (i.e., maxima at 498 and 508 nm, respectively). With a newly developed mouse model (Opn1lw(LIAIS)) expressing a variant of the human L-cone pigment (561 nm) instead of the mouse M-opsin, the absorption spectra are substantially separated, allowing retinal physiology to be studied using silent substitution stimuli. Unlike conventional chromatic isolation methods, this spectral compensation approach can isolate single photoreceptor subtypes without changing the retinal adaptation. We measured flicker electroretinograms in these mutants under ketamine-xylazine sedation with double silent substitution (silent S-cone and either rod or M/L-cones) and obtained robust responses for both rods and (L-)cones. Small signals were yielded in wild-type mice, whereas heterozygotes exhibited responses that were generally intermediate to both. Fundamental response amplitudes and phase behaviors (as a function of temporal frequency) in all genotypes were largely similar. Surprisingly, isolated (L-)cone and rod response properties in the mutant strain were alike. Thus the LIAIS mouse warrants a more comprehensive in vivo assessment of photoreceptor subtype-specific physiology, because it overcomes the hindrance of overlapping spectral sensitivities present in the normal mouse.
authors.affiliation: Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany; Department of Biology, Division of Animal Physiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany;
authors.forename: Tina I
authors.identifier: http://orcid.org/0000-0003-1249-4418
authors.initials: TI
authors.lastname: Tsai
authors.affiliation: Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany; Department of Biology, Division of Animal Physiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany;
authors.forename: Jenny
authors.initials: J
authors.lastname: Atorf
authors.affiliation: Vision Sciences, University of Washington, Seattle, Washington;
authors.forename: Maureen
authors.initials: M
authors.lastname: Neitz
authors.affiliation: Vision Sciences, University of Washington, Seattle, Washington;
authors.forename: Jay
authors.initials: J
authors.lastname: Neitz
authors.affiliation: Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany; Department of Anatomy II, University of Erlangen-Nürnberg, Germany; and School of Optometry and Vision Science, University of Bradford, Bradford, United Kingdom jan.kremers@uk-erlangen.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Kremers
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D004596:Electroretinography; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology*; D014991:Xylazine / Q000494:pharmacology
chemical_list: D000778:Anesthetics, Dissociative; D006993:Hypnotics and Sedatives; D017299:Rod Opsins; C095855:long-wavelength opsin; D014991:Xylazine; D007649:Ketamine
keywords: keywords electrophysiology; mouse; photoreceptors; silent substitution