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Improved daylight vision following AAV-mediated expression of R9AP in murine rod photoreceptors

View ORCID ProfileKoji M. Nishiguchi, Kosuke Fujita, Enrico Cristante, James W. Bainbridge, Ronald H. Douglas, Toru Nakazawa, Alexander J. Smith, Robin R. Ali
doi: https://doi.org/10.1101/2020.02.19.955765
Koji M. Nishiguchi
1Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK
2Department of Advanced Ophthalmic Medicine, Graduate School of Medicine, Tohoku University, Sendai, 980-8574, Japan
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  • ORCID record for Koji M. Nishiguchi
Kosuke Fujita
3Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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Enrico Cristante
1Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK
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James W. Bainbridge
1Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK
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Ronald H. Douglas
4Division of Optometry & Visual Science, City, University of London, Northampton Square, London EC1V 0HB, UK
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Toru Nakazawa
2Department of Advanced Ophthalmic Medicine, Graduate School of Medicine, Tohoku University, Sendai, 980-8574, Japan
3Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
5Department of Ophthalmology, Graduate School of Medicine, Tohoku University, Sendai, 980-8574, Japan
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Alexander J. Smith
1Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK
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Robin R. Ali
1Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK
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  • For correspondence: r.ali@ucl.ac.uk
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Abstract

Cone photoreceptors mediate daylight vision and are the primary cells responsible for vision in humans. Cone dysfunction leads to poor quality daylight vision because rod photoreceptors become saturated and non-functional at high light levels. Here we demonstrate that in mice lacking cone function, AAV-mediated over-expression of Rgs9-anchor protein (R9AP), a critical component of the GTPase complex that mediates the deactivation of the phototransduction cascade, results in desensitization of rod function and a “photopic shift” of the rod-driven electroretinogram. This treatment enables rods to respond to brighter light (up to ∼2.0 log) with increased visually-evoked cortical responses to high intensity stimulation. These results suggest that AAV-mediated transfer of R9ap into rods might be used to improve daylight vision in humans visually handicapped by cone dysfunction.

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Posted February 20, 2020.
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Improved daylight vision following AAV-mediated expression of R9AP in murine rod photoreceptors
Koji M. Nishiguchi, Kosuke Fujita, Enrico Cristante, James W. Bainbridge, Ronald H. Douglas, Toru Nakazawa, Alexander J. Smith, Robin R. Ali
bioRxiv 2020.02.19.955765; doi: https://doi.org/10.1101/2020.02.19.955765
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Improved daylight vision following AAV-mediated expression of R9AP in murine rod photoreceptors
Koji M. Nishiguchi, Kosuke Fujita, Enrico Cristante, James W. Bainbridge, Ronald H. Douglas, Toru Nakazawa, Alexander J. Smith, Robin R. Ali
bioRxiv 2020.02.19.955765; doi: https://doi.org/10.1101/2020.02.19.955765

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