Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants
| العنوان: | Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants |
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| المؤلفون: | Robert F. Mullins, Budd A. Tucker, Emily E. Kaalberg, John H. Fingert, Erin R Burnight, Edwin M. Stone, Ian C. Han, Luke A Wiley, Timothy M. Boyce |
| المصدر: | J Ocul Pharmacol Ther |
| بيانات النشر: | Mary Ann Liebert Inc, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Retinal Ganglion Cells, viruses, Genetic enhancement, Ependymoglial Cells, Genetic Vectors, Retinal explants, Biology, Retinal ganglion, Retina, Adenoviridae, Viral vector, Rats, Sprague-Dawley, chemistry.chemical_compound, Animals, Humans, Pharmacology (medical), Tropism, Aged, Aged, 80 and over, Pharmacology, Retinal, Genetic Therapy, Original Articles, Rats, Cell biology, Ophthalmology, chemistry |
| الوصف: | 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 × 10(6) 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. |
| تدمد: | 1557-7732 1080-7683 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0b6b59e7a8e794c3752a598654cec52Test https://doi.org/10.1089/jop.2021.0057Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a0b6b59e7a8e794c3752a598654cec52 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577732 10807683 |
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