June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Suprachoroidal Injections of AAV for Retinal Gene Delivery in mouse
Author Affiliations & Notes
  • Bo Tian
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Jun Xie
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Wenqi Su
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Shuo Sun
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Qin Su
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Guangping Gao
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Haijiang Lin
    University of Massachusetts Medical School, Worcester, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Bo Tian, None; Jun Xie, None; Wenqi Su, None; Shuo Sun, None; Qin Su, None; Guangping Gao, None; Haijiang Lin, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1177. doi:
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    • Get Citation

      Bo Tian, Jun Xie, Wenqi Su, Shuo Sun, Qin Su, Guangping Gao, Haijiang Lin; Suprachoroidal Injections of AAV for Retinal Gene Delivery in mouse. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1177.

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

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Abstract

Purpose : Recombinant Adeno-Associated Virus (AAV) gene therapy has remarkably advanced in the treatment of retinal diseases due to its safety and efficacy. Each of the AAV administration routes of delivery to the retina confers unique advantages and limitations. Intravitreal delivery is hindered by the internal limiting membrane barrier for primates, and induces humoral immune response, while subretinal delivery necessitates invasive surgery and generates retinal detachment. In contrst, suprachoroidal (SC) injection, targeting the space between the sclera and choroid, is emerging as a novel approach to deliver AAV into the posterior segment of the eye with least invasive procedure, but this route has not been fully elucidated in mouse model for different AAV serotypes. Here, we investigated the transduction efficiency, cell tropism and bio-distribution in mouse retina, for three serotypes of AAV via SC administration.

Methods : EGFP reporter gene driven by the ubiquitous promoter CBA was packaged in three conventionally used AAV serotypes. In 12-week old C57BL/6J mice, SC inject 1.0μl Fluorescein Sodium (1.0 x 10E-6 %) or the three scAAVs-CBA-EGFP solution respectively. Retinal structure was imaged pre-, post-injection and 1.5 weeks post-injection by fundoscopy and optical coherence tomography (OCT). Transduction efficiency and tropism was assessed 1.5 weeks post injection by fundoscopy and histology. Immune response was evaluated by immunostaining for Iba1 macrophages, CD45+ leukocyte and CD3+ T cells.

Results : The retina structure was tracked and shown the successful injection into the suprachoroidal compartment. Transduction of outer retina, and retinal pigment epithelium was observed with these three AAV serotypes by SC delivered, and 3 AAVs displayed varied efficiency and cell specificity. Meanwhile, the activation of inflammatory cells was observed pending on doses adopted. To be noted, retinal detachment was successfully evaded, together with a widespread distribution of the transduction in mouse retina layers.

Conclusions : This study unveils the feasibility of SC injection in mouse, facilitating the proof-of-concept and pre-clinical studies of retinal gene therapy in mouse models. Without the complications of retinal detachment, SC administration is a preferred route to deliver AAV into outer retina layers in comparison with subretinal route. SC injection can serve as a alternative intraocular delivery methods of AAV.

This is a 2021 ARVO Annual Meeting abstract.

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