June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Protein Expression and Tolerability after a Secondary Subretinal Injection of an AAV Vector to the Ipsilateral Eye in Non-human Primates
Author Affiliations & Notes
  • Ryan F. Boyd
    Charles River Laboratories, Mattawan, Michigan, United States
  • Thomas S. Vihtelic
    Charles River Laboratories, Mattawan, Michigan, United States
  • Judith A. Newmark
    Applied Genetic Technologies Corporation, Cambridge, Massachusetts, United States
  • Adrian M Timmers
    Applied Genetic Technologies Corporation, Cambridge, Massachusetts, United States
  • Mark S. Shearman
    Applied Genetic Technologies Corporation, Cambridge, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ryan Boyd, None; Thomas Vihtelic, None; Judith Newmark, AGTC (E); Adrian Timmers, AGTC (E); Mark Shearman, AGTC (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2461. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ryan F. Boyd, Thomas S. Vihtelic, Judith A. Newmark, Adrian M Timmers, Mark S. Shearman; Protein Expression and Tolerability after a Secondary Subretinal Injection of an AAV Vector to the Ipsilateral Eye in Non-human Primates. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2461.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Secondary subretinal injection of an AAV vector to the contralateral eye is an accepted practice in preclinical and clinical studies. Minimal information is available, however, on the expression and safety outcomes of performing a secondary subretinal injection of AAV vector to the same eye. We used non-human primates to investigate the feasibility of performing a subretinal reinjection to the same eye.

Methods : Cynomolgus macaques were divided into low dose (n=4) and high dose groups (n=4). Both eyes were given a single subretinal injection of AAV vector including a photoreceptor specific promoter and hGFP reporter, in either a central or peripheral location on Day 1 (50% of eyes to each location). During Week 8 the left eye was given a second subretinal injection of the same vector at high dose, using the opposite location (central or peripheral) from the first injection. At Week 16 the animals were sacrificed, and the eyes processed for immunohistochemistry of hGFP and histopathological assessment by a veterinary pathologist. Ophthalmic exams were performed throughout the study to assess tolerability and inflammation, and fundus autofluorescence confocal scanning laser ophthalmoscopy (cSLO) was performed to evaluate hGFP expression. Neutralizing antibodies, fluorescein angiography, and clinical pathology were also assessed.

Results : Ocular examinations showed a minimal level of inflammation after the first injection. Similarly, no apparent increase in inflammation was recorded following the second subretinal injection. Quantitative analysis of fundus autofluorescence cSLO images demonstrated increasing hGFP expression after the first injection. Quantitative analysis of hGFP expression following the second injection showed a high level of hGFP expression in the first location and steadily increasing hGFP expression in the second location.

Conclusions : Secondary subretinal injection of an AAV vector to the ipsilateral eye was well tolerated in non-human primates and did not appear to inhibit transgene expression. The option to perform additional subretinal injections provides patients with a better chance for effective therapy if an initial injection was ineffective or failed, additional retinal regions require treatment, or if transgene expression or efficacy diminishes over time.

This is a 2020 ARVO Annual Meeting abstract.

×
×

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.

×