Restoration of Vision with Ectopic Expression of Human Rod Opsin

被引:130
作者
Cehajic-Kapetanovic, Jasmina [1 ,2 ]
Eleftheriou, Cyril [3 ]
Allen, Annette E. [3 ]
Milosavljevic, Nina [3 ]
Pienaar, Abigail [3 ]
Bedford, Robert [3 ]
Davis, Katherine E. [3 ]
Bishop, Paul N. [1 ,2 ]
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
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会; 欧洲研究理事会;
关键词
RESTORES VISUAL RESPONSES; RETINAL GANGLION-CELLS; ON-BIPOLAR CELLS; RETINITIS-PIGMENTOSA; LIGHT ADAPTATION; BLIND MICE; PHOTORECEPTOR DEGENERATION; MOUSE MODEL; MELANOPSIN; TRANSDUCTION;
D O I
10.1016/j.cub.2015.07.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2111 / 2122
页数:12
相关论文
共 36 条
  • [1] 11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors
    Ablonczy, Z
    Crouch, RK
    Goletz, PW
    Redmond, TM
    Knapp, DR
    Ma, JX
    Rohrer, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) : 40491 - 40498
  • [2] Melanopsin-Driven Light Adaptation in Mouse Vision
    Allen, Annette E.
    Storchi, Riccardo
    Martial, Franck P.
    Petersen, Rasmus S.
    Montemurro, Marcelo A.
    Brown, Timothy M.
    Lucas, Robert J.
    [J]. CURRENT BIOLOGY, 2014, 24 (21) : 2481 - 2490
  • [3] Human melanopsin forms a pigment maximally sensitive to blue light (λmax ≈ 479 nm) supporting activation of Gq/11 and Gi/o signalling cascades
    Bailes, Helena J.
    Lucas, Robert J.
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2013, 280 (1759)
  • [4] Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration
    Bi, AD
    Cui, JJ
    Ma, YP
    Olshevskaya, E
    Pu, ML
    Dizhoor, AM
    Pan, ZH
    [J]. NEURON, 2006, 50 (01) : 23 - 33
  • [5] The mouse light/dark box test
    Bourin, M
    Hascoët, M
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 463 (1-3) : 55 - 65
  • [6] Melanopsin-Based Brightness Discrimination in Mice and Humans
    Brown, Timothy M.
    Tsujimura, Sei-ichi
    Allen, Annette E.
    Wynne, Jonathan
    Bedford, Robert
    Vickery, Graham
    Vugler, Anthony
    Lucas, Robert J.
    [J]. CURRENT BIOLOGY, 2012, 22 (12) : 1134 - 1141
  • [7] Melanopsin Contributions to Irradiance Coding in the Thalamo-Cortical Visual System
    Brown, Timothy M.
    Gias, Carlos
    Hatori, Megumi
    Keding, Sheena R.
    Semo, Ma'ayan
    Coffey, Peter J.
    Gigg, John
    Piggins, Hugh D.
    Panda, Satchidananda
    Lucas, Robert J.
    [J]. PLOS BIOLOGY, 2010, 8 (12)
  • [8] Optogenetic therapy for retinitis pigmentosa
    Busskamp, V.
    Picaud, S.
    Sahel, J. A.
    Roska, B.
    [J]. GENE THERAPY, 2012, 19 (02) : 169 - 175
  • [9] Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa
    Busskamp, Volker
    Duebel, Jens
    Balya, David
    Fradot, Mathias
    Viney, Tim James
    Siegert, Sandra
    Groner, Anna C.
    Cabuy, Erik
    Forster, Valerie
    Seeliger, Mathias
    Biel, Martin
    Humphries, Peter
    Paques, Michel
    Mohand-Said, Saddek
    Trono, Didier
    Deisseroth, Karl
    Sahel, Jose A.
    Picaud, Serge
    Roska, Botond
    [J]. SCIENCE, 2010, 329 (5990) : 413 - 417
  • [10] Light-sensitive coupling of rhodopsin and melanopsin to Gi/o and Gq signal transduction in Caenorhabditis elegans
    Cao, Pengxiu
    Sun, Wenyu
    Kramp, Kristopher
    Zheng, Maohua
    Salom, David
    Jastrzebska, Beata
    Jin, Hui
    Palczewski, Krzysztof
    Feng, Zhaoyang
    [J]. FASEB JOURNAL, 2012, 26 (02) : 480 - 491