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Anabel Doumad, Blerta Cooper, Kristin Mathias, Sven Moller-Tank, Ann Ligocki, Carmelo Romano; Intracameral Administration of AAV Serotypes and their Ocular Tissue Tropism . Invest. Ophthalmol. Vis. Sci. 2019;60(9):3365.
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© ARVO (1962-2015); The Authors (2016-present)
Adeno-associated virus (AAV) is a delivery platform for gene therapy being used for ocular treatments. Although there is much information regarding AAV serotype tropism for the posterior segment of the eye, there is less documentation for the anterior segment. This study assessed the anterior tissue transduction and ocular tropism of AAV serotypes 2, 5, 6, 8, and 9 in mice.
AAV-eGFP serotypes were delivered at 1.5e10 vg (1.5uL) via intracameral injections (IC) into male Jackson C57Bl/6J mice (10-11 week). Experimental mice were bilaterally injected with AAV-eGFP and control mice were bilaterally injected with PBS containing 0.001% pluronic acid. eGFP expression was assessed in vivo (FA/OCT imaging; Heidelberg) and ex vivo with histology at 4 timepoints over 12 weeks (days 14, 28, 56 & 84) and ELISA for eGFP at day 84.
Transduction efficiency and tropism varied depending on the AAV serotype used. Using FA/OCT, we were able to determine regions of AAV transduction after IC administration. We found that AAV2, 6, 8 and 9 target both the posterior and anterior segments of the eye after IC administration with AAV6 showing the strongest eGFP expression in the anterior segment, whereas AAV5 targets only anterior ocular tissues.
Using in vivo imaging, transduction efficiency and tropism of AAV serotypes can be measured over a time-course study and are predictive of histological studies. These data suggest that AAV5, 6, and 8 have a strong tropism for anterior regions after IC injections. Additionally, IC injections are also capable of delivering AAVs to the posterior segment.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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