Restoration of Vision with Ectopic Expression of Human Rod Opsin
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作者:
Cehajic-Kapetanovic, Jasmina
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Univ Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Manchester Royal Eye Hosp, CMFT, Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Cehajic-Kapetanovic, Jasmina
[1
,2
]
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Eleftheriou, Cyril
[3
]
Allen, Annette E.
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机构:
Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Allen, Annette E.
[3
]
Milosavljevic, Nina
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机构:
Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Milosavljevic, Nina
[3
]
Pienaar, Abigail
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Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Pienaar, Abigail
[3
]
Bedford, Robert
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Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Bedford, Robert
[3
]
Davis, Katherine E.
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Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Davis, Katherine E.
[3
]
Bishop, Paul N.
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Univ Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Manchester Royal Eye Hosp, CMFT, Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Bishop, Paul N.
[1
,2
]
Lucas, Robert J.
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Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, EnglandUniv Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
Lucas, Robert J.
[3
]
机构:
[1] Univ Manchester, Ctr Ophthalmol & Vis Sci, Inst Human Dev, Manchester M13 9PT, Lancs, England
[2] Manchester Royal Eye Hosp, CMFT, Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, England
[3] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a nonselective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (approximate to 50-100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration.
机构:
Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USAFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
Deisseroth, Karl
Sahel, Jose A.
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机构:
INSERM, UMR S968, Inst Vis, Paris, France
Univ Paris 06, UMR S968, Inst Vis, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, Ctr Invest Clin 503, Paris, France
Fdn Ophtalmol Adolphe de Rothschild, Paris, FranceFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
Sahel, Jose A.
Picaud, Serge
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, UMR S968, Inst Vis, Paris, France
Univ Paris 06, UMR S968, Inst Vis, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Fdn Ophtalmol Adolphe de Rothschild, Paris, FranceFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Cao, Pengxiu
Sun, Wenyu
论文数: 0引用数: 0
h-index: 0
机构:
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Sun, Wenyu
Kramp, Kristopher
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机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Kramp, Kristopher
Zheng, Maohua
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h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Zheng, Maohua
Salom, David
论文数: 0引用数: 0
h-index: 0
机构:
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Salom, David
Jastrzebska, Beata
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机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Jastrzebska, Beata
Jin, Hui
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h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Jin, Hui
Palczewski, Krzysztof
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机构:
Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Palczewski, Krzysztof
Feng, Zhaoyang
论文数: 0引用数: 0
h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Xi An Jiao Tong Univ, Dept Physiol, Coll Med, Xian 710049, Peoples R ChinaCase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
机构:
Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USAFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
Deisseroth, Karl
Sahel, Jose A.
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, UMR S968, Inst Vis, Paris, France
Univ Paris 06, UMR S968, Inst Vis, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, Ctr Invest Clin 503, Paris, France
Fdn Ophtalmol Adolphe de Rothschild, Paris, FranceFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
Sahel, Jose A.
Picaud, Serge
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, UMR S968, Inst Vis, Paris, France
Univ Paris 06, UMR S968, Inst Vis, F-75012 Paris, France
CNRS, UMR 7210, F-75012 Paris, France
Fdn Ophtalmol Adolphe de Rothschild, Paris, FranceFriedrich Miescher Inst Biomed Res, Neural Circuit Labs, Basel, Switzerland
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Cao, Pengxiu
Sun, Wenyu
论文数: 0引用数: 0
h-index: 0
机构:
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Sun, Wenyu
Kramp, Kristopher
论文数: 0引用数: 0
h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Kramp, Kristopher
Zheng, Maohua
论文数: 0引用数: 0
h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Zheng, Maohua
Salom, David
论文数: 0引用数: 0
h-index: 0
机构:
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Salom, David
Jastrzebska, Beata
论文数: 0引用数: 0
h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Jastrzebska, Beata
Jin, Hui
论文数: 0引用数: 0
h-index: 0
机构:Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Jin, Hui
Palczewski, Krzysztof
论文数: 0引用数: 0
h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Polgenix Inc, Cleveland, OH USACase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Palczewski, Krzysztof
Feng, Zhaoyang
论文数: 0引用数: 0
h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA
Xi An Jiao Tong Univ, Dept Physiol, Coll Med, Xian 710049, Peoples R ChinaCase Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA