Visual properties of transgenic rats harboring the channelrhodopsin-2 gene regulated by the thy-1.2 promoter

• Published in: PloS one Vol. 4; no. 11; p. e7679
• Main Authors: Tomita, Hiroshi, Sugano, Eriko, Fukazawa, Yugo, Isago, Hitomi, Sugiyama, Yuka, Hiroi, Teru, Ishizuka, Toru, Mushiake, Hajime, Kato, Megumi, Hirabayashi, Masumi, Shigemoto, Ryuichi, Yawo, Hiromu, Tamai, Makoto
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.11.2009; Public Library of Science (PLoS)
• Subjects: Albinism; Algae; Animals; Animals, Genetically Modified; Antigens; Apoptosis; Behavior, Animal; Biochemistry; Brain; Brain - metabolism; Brain research; Cell Biology/Gene Expression; Cell Biology/Neuronal Signaling Mechanisms; Cytokines; Degeneration; Deoxyribonucleic acid; Developmental biology; DNA; Frequency dependence; Gene expression; Gene Expression Regulation; Genes; Genetic engineering; Genetics and Genomics/Gene Therapy; Growth factors; Interdisciplinary aspects; Life sciences; Light; Medicine; Mice; Models, Biological; Neurodegeneration; Neurons - metabolism; Neuroscience; Neuroscience/Behavioral Neuroscience; Neuroscience/Natural and Synthetic Vision; Neurosciences; Ophthalmology/Inherited Eye Disorders; Ophthalmology/Macular Disorders; Ophthalmology/Retinal Disorders; Photoactivation; Photoreception; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptors; Physiology; Physiology/Neuronal Signaling Mechanisms; Physiology/Sensory Systems; Promoter Regions, Genetic; Rats; Retina; Retinal degeneration; Retinal ganglion cells; Retinal Ganglion Cells - metabolism; Retinitis; Retinitis pigmentosa; Rhodopsin; Rhodopsin - biosynthesis; Rhodopsin - genetics; Rodents; Thy-1 Antigens - genetics; Thy-1 Antigens - metabolism; Transgenic animals; University graduates; Vision; Vision, Ocular; Visual observation; Visual signals; Visual stimuli; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007679

Channelrhodopsin-2 (ChR2), one of the archea-type rhodopsins from green algae, is a potentially useful optogenetic tool for restoring vision in patients with photoreceptor degeneration, such as retinitis pigmentosa. If the ChR2 gene is transferred to retinal ganglion cells (RGCs), which send visual information to the brain, the RGCs may be repurposed to act as photoreceptors. In this study, by using a transgenic rat expressing ChR2 specifically in the RGCs under the regulation of a Thy-1.2 promoter, we tested the possibility that direct photoactivation of RGCs could restore effective vision. Although the contrast sensitivities of the optomotor responses of transgenic rats were similar to those observed in the wild-type rats, they were enhanced for visual stimuli of low-spatial frequency after the degeneration of native photoreceptors. This result suggests that the visual signals derived from the ChR2-expressing RGCs were reinterpreted by the brain to form behavior-related vision.