title: Visual Responses of Photoreceptor-Degenerated Rats Expressing Two Different Types of Channelrhodopsin Genes.
abstract: Optogenetic technologies are expected to be applicable for clinical use in restoring vision. However, the degree of recovered visual function is highly dependent on the function of the chosen optogenetic gene. To investigate the effect on visual function of dual expression of genes with different wavelength sensitivities, we transduced a modified Volvox-derived channelrhodopsin gene (mVChR1) via an adeno-associated virus vector into transgenic rats harbouring the ChR2 gene in retinal ganglion cells. These transgenic rats were given an intraperitoneal injection of N-methyl-N-nitrosourea to induce the degeneration of native photoreceptor cells prior to transduction of mVChR1. Optical coherence tomography images indicated the degeneration of the native photoreceptor cells after the N-methyl-N-nitrosourea injection. Complete loss of function of the native photoreceptor cells was confirmed using electroretinograms. In the ChR2 transgenic rats, visually evoked potentials were clearly detectable in spite of native photoreceptor function abolishment; however the responses were limited to within blue wavelengths. In contrast, the limited wavelength sensitivities were improved by the additional transduction of mVChR1, which exhibited sensitivities to green and red. Thus, the transductions of dual genes encoding channelrhodopsins that exhibit different wavelength sensitivities represents a promising candidate method to expand and to enhance rescued wavelength sensitivities in blind subjects.
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Sato
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.|Soft-Path Engineering Research Center (SPERC), Iwate University Division of Science and Engineering, Morioka 020-8551, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugano
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.
authors.forename: Kitako
authors.initials: K
authors.lastname: Tabata
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sannohe
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.|Soft-Path Engineering Research Center (SPERC), Iwate University Division of Science and Engineering, Morioka 020-8551, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamai
authors.affiliation: Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.|Soft-Path Engineering Research Center (SPERC), Iwate University Division of Science and Engineering, Morioka 020-8551, Japan.|Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomita
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins / Q000235:genetics*; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D005822:Genetic Vectors; D008770:Methylnitrosourea / Q000008:administration & dosage; D062308:Optogenetics; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D041623:Tomography, Optical Coherence; D044446:Volvox / Q000235:genetics
chemical_list: D000075402:Channelrhodopsins; D008770:Methylnitrosourea