Trans-ocular electric current in vivo enhances aav-mediated retinal transduction in large animal eye after intravitreal vector administration

Hongman Song, Yong Zeng, Sheik Pran Babu Sardar Pasha, Ronald A. Bush, Camasamudram Vijayasarathy, Haohua Qian, Lisa Wei, Henry E. Wiley, Zhijian Wu, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: Electric micro-current has been shown to enhance penetration and transduction of adeno-associated viral (AAV) vectors in mouse retina after intravitreal administration. We termed this: “electric-current vector mobility (ECVM).” The present study considered whether ECVM could augment retinal transduction efficiency of intrav-itreal AAV8-CMV-EGFP in normal rabbit and nonhuman primate (NHP) macaque. Potential mechanisms underlying enhanced retinal transduction by ECVM were also studied.Methods: We applied an electric micro-current across the intact eye of normal rabbit and monkey in vivo for a brief period immediately after intravitreal injection of AAV8-CMV-EGFP. Retinal GFP expression was evaluated by fundus imaging in vivo. Retinal immunohistochemistry was performed to assess the distribution of retinal cells trans-duced by the AAV8-EGFP. Basic fibroblast growth factor (bFGF) was analyzed by quantitative RT-polymerase chain reaction (PCR). Müller glial reactivity and inner limiting membrane (ILM) were examined by the glial fibrillary acidic protein (GFAP) and vimentin staining in mouse retina, respectively.Results: ECVM significantly increased the efficiency of AAV reaching and transducing the rabbit retina following intravitreal injection, with gene expression in inner nuclear layer, ganglion cells, and Müller cells. Similar trend of improvement was observed in the ECVM-treated monkey eye. The electric micro-current upregulated bFGF expression in Müller cells and vimentin showed ILM structural changes in mouse retina.Translational Relevance: This work has potential translational relevance to human ocular gene therapy by increasing retinal expression of therapeutic vectors given by intravitreal administration.

Original languageEnglish (US)
Article number28
Pages (from-to)1-13
Number of pages13
JournalTranslational Vision Science and Technology
Volume9
Issue number7
DOIs
StatePublished - 2020

Keywords

  • AAV vector
  • Electric current
  • Gene delivery and expression in the retina
  • Intravitreal administration
  • Large-animal models

ASJC Scopus subject areas

  • Biomedical Engineering
  • Ophthalmology

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