July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Biodistribution and tolerability of rAAV vectors in the anterior chamber for the treatment of primary open angle glaucoma
Author Affiliations & Notes
  • Kristina Ertel
    Cell Biology Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Daniel M. Lipinski
    Ophthalmology and Visual Science, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships   Kristina Ertel, Medical College of Wisconsin (P); Daniel Lipinski, Medical College of Wisconsin (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2922. doi:
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      Kristina Ertel, Daniel M. Lipinski; Biodistribution and tolerability of rAAV vectors in the anterior chamber for the treatment of primary open angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2922.

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

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Purpose : Poor adherence to existing topical treatments for lowering intra-ocular pressure (IOP) is a major risk factor in developing vision compilations in primary open angle glaucoma (POAG). Consequently, developing a long-acting, single use gene therapy to permanently lower IOP would significantly improve visual outcomes and patient quality of life. One barrier to development of such a therapy is the ability to safely and efficiently transduce cells of the anterior chamber. Herein, we evaluate the tropism, safety and tolerability of four recombinant adeno-associated virus (rAAV) serotypes following intracameral injection using in vivoimaging and post-mortem histology.

Methods : C57BL/6J mice were injected with 2.6x109 viral genomes of rAAV2/1, 2/6, 2/9, or 2/2[MAX] packaging a GFP reporter gene driven by a small chicken beta actin promoter (N=20). GFP expression within the anterior chamber was assessed in vivofour weeks post injection using confocal scanning laser ophthalmoscopy (cSLO). Anterior chamber optical coherence tomography (OCT) imaging was used to evaluate corneal health and thickness following rAAV administration. Slit lamp examination and flare scoring was performed to assess inflammatory response to rAAV following intracameral injection. Following in vivoevaluations, eyes from all animals were enucleated and fixed for histological evaluation to confirm rAAV tropism.

Results : Corneal OCT and slit lamp evaluation showed no evidence of inflammation or increased corneal thickness compared to baseline levels. cSLO imaging of rAAV2/6 injected eyes revealed widespread corneal transduction. Injection of rAAV[MAX] and 2/9 also transduced the cornea, while rAAV 2/1 showed transduction of the iris and angle.

Conclusions : Herein, we evaluate the transduction tropism and tolerance of differing rAAV serotypes in the anterior chamber. Importantly, we observed that intracameral administration of rAAV is well tolerated and does not induce an observable immune response or corneal alterations. rAAV2/6 resulted in highly efficient and specific transduction of corneal endothelial cells and may have use in the development of gene therapy treatments for endothelial dystrophies. rAAV2/2[MAX] was additionally able to transduce trabecular meshwork cells, making it an attractive candidate for mediating a gene delivery in glaucoma.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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