September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia – Long Term Follow-up
Author Affiliations & Notes
  • Raaya Ezra-Elia
    Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
  • Elisha Gootwine
    Agricultural Research Organization, The Volcani Center, Beit Dagan, Israel
  • Edward Averbukh
    Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Alexey Obolensky
    Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Alexander Rosov
    Agricultural Research Organization, The Volcani Center, Beit Dagan, Israel
  • Hen Honig
    Agricultural Research Organization, The Volcani Center, Beit Dagan, Israel
  • Shai Sandalon
    Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
  • William Hauswirth
    Department of Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Eyal Banin
    Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Ron Ofri
    Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
  • Footnotes
    Commercial Relationships   Raaya Ezra-Elia, None; Elisha Gootwine, AGTC (F); Edward Averbukh, None; Alexey Obolensky, None; Alexander Rosov, None; Hen Honig, None; Shai Sandalon, None; William Hauswirth, AGTC (P), AGTC (F), AGTC (C); Eyal Banin, AGTC (F); Ron Ofri, None
  • Footnotes
    Support  NIH grant EY021721, FFB, MVRF, RPB, Inc, The US-Israel Binational Science Foundation (2011445), The Chief Scientist Office of the Israeli Ministry of Health, Israel Science Foundation (1257/15), The Israeli Research Association for Eye Health and Blindness Prevention-Lirot, The Macula Vision Research Foundation, and unrestricted awards from The Joseph Alexander Foundation and Yedidut 1 Research Grant.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5149. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Raaya Ezra-Elia, Elisha Gootwine, Edward Averbukh, Alexey Obolensky, Alexander Rosov, Hen Honig, Shai Sandalon, William Hauswirth, Eyal Banin, Ron Ofri; Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia – Long Term Follow-up. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5149.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Recently we reported that unilateral subretinal delivery of an adeno-associated virus serotype 5 (AAV5) vector carrying either mouse (mCNGA3) or human (hCNGA3) cDNA results in recovery of photopic vision in CNGA3-mutant dayblind sheep. Following recent reports that the efficacy of gene therapy in LCA patients starts declining after 6-12 months, our aim was to evaluate long-term treatment efficacy in our treated sheep cohort.

Methods : Animals that underwent mCNGA3 (n=4) or hCNGA3 (n=5) gene augmentation therapy 3.8±0.5 and 3.0±0.2 years ago, respectively, were studied. Photopic vision was evaluated by maze navigation. Cone function was evaluated by light adapted, full-field flash electroretinography. Flicker responses to eight increasing frequencies were recorded and the critical flicker fusion frequency (CFFF) determined.

Results : Mean±SD passage time of mCNGA3- and hCNGA3-treated animals was 4.7±0.6 and 4.0±0.5 seconds, respectively, without any collisions with obstacles. However, when the treated eye was covered, average passage time increased significantly (P<0.0005) to 24.2±9.4 and 23.3±7.3 seconds, respectively, and the number of collisions increased to 1.6±1.3 and 5.8±2.2 in mCNGA3- and hCNGA3-treated animals, respectively. The CFFF of mCNGA3 and hCNGA3-treated eyes was 70±8.2 and 65±5.8 Hz, respectively, compared to 25±5.8 and 32.5±25 Hz in the untreated control eyes (p<0.0005).

Conclusions : A single, subretinal injection of a AAV5 carrying the CNGA3 cDNA resulted in significant improvement in photopic vision and cone function, lasting over 3 years. Our results confirm long-term efficacy and safety of CNGA3 gene therapy in our dayblind sheep model, paving the way for clinical trials in achromatopsia patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

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.

×