May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Responses of Intrinsically-Photosensitive Retinal Ganglion Cells After Melanopsin-Gene Transfection
Author Affiliations & Notes
  • Y. Zhang
    MCB and Center for Brain Science, Harvard University, Cambridge, Massachusetts
  • M. Meister
    MCB and Center for Brain Science, Harvard University, Cambridge, Massachusetts
  • B. S. Pawlyk
    The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • O. V. Bulgakov
    The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • T. Li
    The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • M. A. Sandberg
    The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships Y. Zhang, None; M. Meister, None; B.S. Pawlyk, None; O.V. Bulgakov, None; T. Li, None; M.A. Sandberg, None.
  • Footnotes
    Support NIH grant EY016350 and a Damon Runyon Fellowship (YZ).
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4604. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Y. Zhang, M. Meister, B. S. Pawlyk, O. V. Bulgakov, T. Li, M. A. Sandberg; Responses of Intrinsically-Photosensitive Retinal Ganglion Cells After Melanopsin-Gene Transfection. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4604.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: To determine if transfection of melanopsin into the adult rd/rd mouse retina will increase the sensitivity and/or number of intrinsically-photosensitive retinal ganglion cells (ipRGCs).

Methods:: An AAV-vector carrying a melanopsin and GFP reporter gene (pAAV-OPN4-IZsGreen) driven by a CMV promoter was generated and injected into the vitreous of one eye of adult rd/rd mice. A control GFP-only vector (pAAV-MCS6-IZsGreen) was injected into fellow eyes. Spike responses of retinal ganglion cells to flashing bars of varying intensity and width were recorded with a multi-electrode array.

Results:: AAV-mediated melanopsin expression was detected in up to 30% of RGCs, whereas only ~1% of RGCs express melanopsin endogenously. The distribution of transgenic melanopsin showed the normal association with the plasma membrane. More than 90% of the RGCs were light sensitive in the melanopsin-transfected eyes. Responses were detected at a threshold intensity of ~1012 photons/sec/cm2 and saturated at ~3 x 1014 photons/sec/cm2. The receptive field diameter (FWHM) averaged 97 µm. In control eyes, ~30% of RGCs were light sensitive, with a similar dynamic range and receptive field diameter as in transfected eyes.

Conclusions:: In the retina of adult rd/rd mice, ipRGCs are more numerous than expected based on melanopsin immunocytochemistry. The receptive fields of ipRGCs are smaller than previously-reported dendritic fields, suggesting that melanopsin transduction is restricted to a region close to the soma. Melanopsin transfection may render nearly the entire RGC population photosensitive.

Keywords: gene transfer/gene therapy • ganglion cells • receptive fields 
×
×

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.

×