December 2023
Volume 23, Issue 15
Open Access
Optica Fall Vision Meeting Abstract  |   December 2023
Contributed Session III: AAV-mediated gene therapy for PDE6C achromatopsia: Progress and challenges
Author Affiliations
  • Ala Moshiri
    UC Davis
  • Tawfik Issa
    Baylor College of Medicine
  • Jeffrey Rogers
    Baylor College of Medicine
  • Rui Chen
    Baylor College of Medicine
  • Sara Thomasy
    UC Davis
  • Tim Stout
    Baylor College of Medicine
Journal of Vision December 2023, Vol.23, 81. doi:
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      Ala Moshiri, Tawfik Issa, Jeffrey Rogers, Rui Chen, Sara Thomasy, Tim Stout; Contributed Session III: AAV-mediated gene therapy for PDE6C achromatopsia: Progress and challenges. Journal of Vision 2023;23(15):81.

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

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Purpose: To determine the clinical circumstances under which viral mediated gene therapy can rescue cone function in a nonhuman primate model of PDE6C achromatopsia. Methods: Infant rhesus macaques homozygous for the PDE6C R565Q mutation were generated through a breeding program at the California National Primate Research Center. Homozygotes were treated in the right eye with adeno-associated virus (AAV5) carrying rhesus PDE6C under the control of the PR1.7 cone-specific promoter. The left eye was used as a control. Animals were tested by full-field and multifocal electroretinography. A total of 7 animals have been treated. Results: The virus was found to be safe, but with variable inflammatory response. There were no obvious alterations in retinal lamination in treated eyes. The virus was expressed specifically in cone photoreceptors. Pre- and post-treatment systemic steroids led to minimal to moderate inflammatory response. In general, the gene therapy partially restored the cone responses on ERG within one month of injection in infants, but not in the older animals. If restored, the rescued cone responses were sustained and durable for over a year. Chromatic ERG testing showed restoration of amplitudes in all three cone subtypes. Conclusions: AAV-mediated gene therapy partially restored cone function and was relatively durable. Inflammation and age of administration may be important to outcomes. Similar approaches in human patients may warrant investigation.

 Funding: Funding: NIH NEI U24 EY029904

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