June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Safety and efficacy of recombinant adeno-associated virus (rAAV) mediated transduction in the anterior chamber of the African Green Monkey (Chlorocebus sabaeus)
Author Affiliations & Notes
  • Kristina J Chern
    Cell and Developmental Biology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
    Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Gavin J Marcoe
    Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Kimica Isaac
    RxGen, New Haven, Connecticut, United States
  • Zendorf Gumbs
    RxGen, New Haven, Connecticut, United States
  • Dexter Fahie
    RxGen, New Haven, Connecticut, United States
  • Melissa O'Conner
    RxGen, New Haven, Connecticut, United States
  • Daniel M Lipinski
    Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Footnotes
    Commercial Relationships   Kristina Chern None; Gavin Marcoe None; Kimica Isaac None; Zendorf Gumbs None; Dexter Fahie None; Melissa O'Conner None; Daniel Lipinski None
  • Footnotes
    Support  NEI Grant T32EY014537
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 59 – A0032. doi:
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      Kristina J Chern, Gavin J Marcoe, Kimica Isaac, Zendorf Gumbs, Dexter Fahie, Melissa O'Conner, Daniel M Lipinski; Safety and efficacy of recombinant adeno-associated virus (rAAV) mediated transduction in the anterior chamber of the African Green Monkey (Chlorocebus sabaeus). Invest. Ophthalmol. Vis. Sci. 2022;63(7):59 – A0032.

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

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Abstract

Purpose : Glaucoma is characterized by progressive retinal ganglion cell loss and optic nerve degeneration, and is a leading cause of blindness worldwide. While pharmacological approaches aimed at lowering intraocular pressure (IOP) are effective at preventing vision loss, patient compliance is extremely poor. As such, there is a need for the development of a long-acting IOP-lowering gene therapy for glaucoma. Herein, we assess the tolerability and tropism of three recombinant adeno-associated virus (rAAV) vectors when injected intracamerally in a non-human primate (NHP) model.

Methods : Six sero-negative African Green Monkeys underwent ophthalmic examinations, including optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (cSLO), tonometry, pachymetry and slit lamp imaging, to establish pre-injection baseline values. Eyes (N=12) were randomized and injected intracamerally with either a high (1x1012vg) or low (1x1011vg) dose of rAAV2/2[MAX], 2/6 or 2/9 packaging a ubiquitously expressing green fluorescent protein (GFP) reporter, with the contralateral eye left uninjected as a control. Assessments were repeated 1, 3, 7, 14, 21, 28, 35, 42 and 49 days post-injection at which point eyes were enucleated for histology.

Results : Transient increase in IOP was observed in all rAAV treated eyes immediately following vector injection, with pressures returning to normal by day 7. Slit lamp bimicroscopy revealed increased inflammation as evident by increased cell counts immediately following injection, as well as a secondary phase of inflammation 14-21 days after injection, which both resolved spontaneously without pharmacological intervention. No permanent alteration in retinal volume or appearance was observed in any rAAV treatment eyes via OCT or SLO. Corneal thickness remained constant in 11/12 injected eyes. Specular microscopy at day 42 indicated in all injected groups there were no changes in endothelial health. cSLO imaging at D42 revealed fluorescence signal in several eyes indicative of GFP expression; histology confirmed signal in the lens capsule, iris, and iridocorneal angle.

Conclusions : Together the results indicate that intracameral administration of rAAV appears to be well tolerated in naïve NHPs, leading to transduction of anterior chamber structures and may be relevant for the treatment of glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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