Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants

Ian C Han; Erin R Burnight; Emily E Kaalberg; Timothy M Boyce; Edwin M Stone; John H Fingert; Robert F Mullins; Budd A Tucker; Luke A Wiley

doi:10.1089/jop.2021.0057

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Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants

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Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants

Ian C Han, Erin R Burnight, Emily E Kaalberg, Timothy M Boyce, Edwin M Stone, John H Fingert, Robert F Mullins, Budd A Tucker and Luke A Wiley

Journal of ocular pharmacology and therapeutics, Vol.37(10), pp.575-579

10/01/2021

DOI: 10.1089/jop.2021.0057

PMID: 34597181

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https://www.ncbi.nlm.nih.gov/pmc/articles/8713574View

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Abstract

Purpose: Despite numerous recent advances in retinal gene therapy using adeno-associated viruses (AAVs) as delivery vectors, there remains a crucial need to identify viral vectors with the ability to transduce specific retinal cell types and that have a larger carrying capacity than AAV. In this study, we evaluate the retinal tropism of 2 chimeric helper-dependent adenoviruses (HDAds), helper-dependent adenovirus serotype 5 (HDAd5)/3 and HDAd5/35, both ex vivo using human retinal explants and in vivo using rats. Methods: We transduced cultured human retinal explants with HDAd5/3 and HDAd5/35 carrying an eGFP vector and evaluated tropism and transduction efficiency using immunohistochemistry. To assess in vivo transduction efficiency, subretinal injections were performed in wild-type Sprague-Dawley rats. For both explants and subretinal injections, we delivered 10 μL (1 × 106 vector genomes/mL) and assessed tropism at 7- and 14-days post-transduction, respectively. Results: HDAd5/3 and HDAd5/35 both transduced human retinal ganglion cells (RGCs) and Müller cells, but not photoreceptors, in human retinal explants. However, subretinal injections in albino rats resulted in transduction of the retinal pigmented epithelium only, highlighting species-specific differences in retinal tropism and the value of a human explant model when testing vectors for eventual human gene therapy. Conclusions: Chimeric HDAds are promising candidates for the delivery of large genes, multiple genes, or neuroprotective factors to Müller cells and RGCs. These vectors may have utility for targeted therapy of neurodegenerative diseases primarily involving retinal ganglion or Müller cell types, such as glaucoma or macular telangiectasia type 2.

Details

Title: Subtitle: Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants
Creators: Ian C Han - University of Iowa
Erin R Burnight - University of Iowa
Emily E Kaalberg - University of Iowa
Timothy M Boyce - University of Iowa
Edwin M Stone - University of Iowa
John H Fingert - University of Iowa
Robert F Mullins - University of Iowa
Budd A Tucker - University of Iowa
Luke A Wiley - University of Iowa
Resource Type: Journal article
Publication Details: Journal of ocular pharmacology and therapeutics, Vol.37(10), pp.575-579
DOI: 10.1089/jop.2021.0057
PMID: 34597181
NLM abbreviation: J Ocul Pharmacol Ther
ISSN: 1080-7683
eISSN: 1557-7732
Language: English
Date published: 10/01/2021
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984187138302771

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