April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Genetic Reactivation of Cone Photoreceptors Restores Complex Visual Responses in Retinitis Pigmentosa - Part 3
Author Affiliations & Notes
  • D. Balya
    Neurobiology, Friedrich Miescher Inst, Basel, Switzerland
  • V. Busskamp
    Neurobiology, Friedrich Miescher Inst, Basel, Switzerland
  • J. Duebel
    Neurobiology, Friedrich Miescher Inst, Basel, Switzerland
  • M. W. Seeliger
    Division of Ocular Neurodegeneration, Ctr Ophthalmology Inst Ophthalmic Research, Tuebingen, Germany
  • P. Humphries
    Ocular Genetics Unit, Trinity College Dublin, Dublin, Ireland
  • M. Biel
    7Center for Integrated Protein Science and Department of Pharmacy, Ludwig Maximilians Universität, Munich, Germany
  • K. Deisseroth
    Department of Bioengineering, Stanford University, Stanford, California
  • J. A. Sahel
    UMR-S 968, Institut de la Vision, Paris, France
  • S. A. Picaud
    Institut de la Vision, INSERM, Paris, France
  • B. Roska
    Neurobiology, Friedrich Miescher Inst, Basel, Switzerland
  • Footnotes
    Commercial Relationships  D. Balya, None; V. Busskamp, None; J. Duebel, None; M.W. Seeliger, None; P. Humphries, None; M. Biel, None; K. Deisseroth, None; J.A. Sahel, None; S.A. Picaud, None; B. Roska, None.
  • Footnotes
    Support  Friedrich Miescher Institute funds, Nicop ONR, Marie Curie Actions, EU HEALTH-F2-223156, Agence National de la recherché (MEDINAS, RETINE)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3297. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      D. Balya, V. Busskamp, J. Duebel, M. W. Seeliger, P. Humphries, M. Biel, K. Deisseroth, J. A. Sahel, S. A. Picaud, B. Roska; Genetic Reactivation of Cone Photoreceptors Restores Complex Visual Responses in Retinitis Pigmentosa - Part 3. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3297.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : In retinal degenerative diseases like Retinitis pigmentosa (RP) rod photoreceptors die early. Light-insensitive, morphologically altered cone photoreceptors persist. It is unknown if these cones are accessible for therapeutic interventions. We evaluated the potential of a red-light sensitive chloride pump in cones to substitute for the native phototransduction cascade and restore their light sensitivity in mouse models of RP.

Methods: : We used adeno-associated-virus (AAV)-mediated gene transfer to express an archaebacterial halorhodopsin (eNpHR) specifically in cones in two mouse models of RP (poster part 1). To test if eNpHR is functional in treated retinas we recorded light responses (poster part 2) from photoreceptors, ganglion cells and the visual cortex, and performed behavioral experiments.

Results: : Resensitized photoreceptors activate retinal cone pathways, drive sophisticated retinal circuit functions including directional selectivity, activate cortical circuits and mediate visually guided behaviors. The increased performance depends on the level of illumination in the dark-light box. In the optomotor reflex test, treated mice perform better than control at a variety of drum speeds.

Conclusions: : Our results demonstrate that, despite the diverse genetic origin of RP, the targeted expression of a single gene can restore significant functionality to the visual system following degenerative changes. Light-induced activity was observed at the ganglion cell level, in the visual cortex and at the behavioral level.

Keywords: gene transfer/gene therapy • retinal degenerations: cell biology • photoreceptors 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.