Optogenetic Retinal Gene Therapy with the Light Gated GPCR Vertebrate Rhodopsin

  • Benjamin M. Gaub
  • Michael H. Berry
  • Meike Visel
  • Amy Holt
  • Ehud Y. Isacoff
  • John G. FlanneryEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1715)


In retinal disease, despite the loss of light sensitivity as photoreceptors die, many retinal interneurons survive in a physiologically and metabolically functional state for long periods. This provides an opportunity for treatment by genetically adding a light sensitive function to these cells. Optogenetic therapies are in development, but, to date, they have suffered from low light sensitivity and narrow dynamic response range of microbial opsins. Expression of light-sensitive G protein coupled receptors (GPCRs), such as vertebrate rhodopsin , can increase sensitivity by signal amplification, as shown by several groups. Here, we describe the methods to (1) express light gated GPCRs in retinal neurons, (2) record light responses in retinal explants in vitro, (3) record cortical light responses in vivo, and (4) test visually guided behavior in treated mice.

Key words

Retinitis pigmentosa Congenital blindness Retinal gene therapy Optogenetics Translational medicine Visual prosthetics Light-gated receptors 


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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Benjamin M. Gaub
    • 1
  • Michael H. Berry
    • 2
  • Meike Visel
    • 2
  • Amy Holt
    • 2
  • Ehud Y. Isacoff
    • 2
    • 3
    • 4
  • John G. Flannery
    • 5
    • 6
    • 7
    Email author
  1. 1.Department of Biosystems Science and Engineering (D-BSSE)Eidgenössische Technische Hochschule (ETH) ZürichBaselSwitzerland
  2. 2.Department of Molecular and Cell BiologyUniversity of California BerkeleyBerkeleyUSA
  3. 3.Physical Bioscience DivisionLawrence Berkeley National LaboratoryBerkeleyUSA
  4. 4.Helen Wills Neuroscience InstituteUniversity of California BerkeleyBerkeleyUSA
  5. 5.Vision Science Graduate Group, School of OptometryUniversity of CaliforniaBerkeleyUSA
  6. 6.The Helen Wills Neuroscience Institute, University of CaliforniaBerkeleyUSA
  7. 7.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkeleyUSA

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