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Peripapillary Intravitreal Injection Improves AAV-Mediated Retinal Transductionopen access

Authors
Madrakhimov, Sanjar BatirovichYang, Jin YoungAhn, Dong HyuckHan, Jung WooHa, Tae HoPark, Tae Kwann
Issue Date
12-Jun-2020
Publisher
Nature Publishing Group
Citation
Molecular Therapy - Methods and Clinical Development, v.17, pp 647 - 656
Pages
10
Journal Title
Molecular Therapy - Methods and Clinical Development
Volume
17
Start Page
647
End Page
656
URI
https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/19498
DOI
10.1016/j.omtm.2020.03.018
ISSN
2329-0501
Abstract
The intravitreal (IVT) injection method is a choice when targeting the inner retina for gene therapy. However, the transduction efficiency of adeno-associated virus (AAV) vectors administered by the IVT route is usually low and may be affected by several factors. To improve the transduction efficiency, we developed a novel illuminated long-needle attached injection system and injected AAV2-CMV (cytomegalovirus)-EGFP in front of the retina in rabbit eyes. Ophthalmological examinations were performed and the levels of pro-inflammatory cytokines in the aqueous humor were assessed at the baseline and 1 month, and the results were compared with those of the conventional injection method. Retinal tissues were used for immunohistochemistry. In the ophthalmological examinations, no significant inflammatory signs were detected in both groups, except for transient, mild hyperemia. In the tissues of the rabbits in the peripapillary injection group, significantly increased GFP expression was detected at the ganglion cell and the inner nuclear layers (p < 0.01). There were no differences between groups in glial activation and expressions of interleukin (IL)-6 and IL-8. These results suggest that peripapillary IVT injection in front of the retina would be safe and efficiently transduce viral vectors into the retina of large animals and is considered as a potential method for use in clinical trials.
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