Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection

Giove, Thomas J.; Sena-Esteves, Miguel; Eldred, William D.

doi:10.1016/j.exer.2010.08.011

Cited by 27Virus-based gene therapy researchRetinal Development and DisordersRNA Interference and Gene Delivery

Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection

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Giove, Thomas J., Sena-Esteves, Miguel, Eldred, William D.·2010·Experimental Eye Research

DOI 10.1016/j.exer.2010.08.011PMC PMC2962726

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Abstract

Adeno-associated virus (AAV) is a proven, safe and effective vector for gene delivery in the retina. There are over 100 serotypes of AAV, and AAV2 through AAV9 have been evaluated in the retina. Each AAV serotype has different cell tropism and transduction efficiency. Intravitreal injections of AAV into the eye tend to transduce cells in the ganglion cell layer (GCL), while subretinal injections tend to transduce retinal pigment epithelium and photoreceptors. Efficient transduction of the inner retina beyond the GCL is not well established with the current methodologies and serotypes used to date. In this study, we compared the cellular tropism of AAVrh8 and AAVrh10 vectors encoding enhanced green fluorescent protein (EGFP) using intravitreal injections. We found that AAVrh8 largely transduced cells in the GCL and also amacrine cells in the inner nuclear layer (INL), as well as Müller and horizontal cells. Inner retinal transduction with AAVrh10 was similar to AAVrh8, but AAVrh10 appeared to also transduce bipolar cells. The transduction efficiency as measured by the intensity of EGFP signal was 3.5 fold higher in horizontal cells transduced with AAVrh10 than AAVrh8. Glial fibrillary accessory protein (GFAP) levels were increased in Müller cells in transduced areas for both serotypes. The results of this study suggest that AAVrh8 and AAVrh10 may be excellent vector candidates to deliver genetic material to the INL, particularly for amacrine and horizontal cells, however they may also cause cellular stress as shown by increased glial GFAP expression.

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Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1 KO and Rho KO mice (XLRS and RP models, respectively) compared to wild-type mice.
“Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1 KO and Rho KO mice (XLRS and RP models, respectively) compared to wild-type mice [310,311].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [311]
The Results section (page not available in our copy) reports that intravitreal AAVrh10 transduced INL cells and appeared to transduce some photoreceptors and retinal pigment epithelium. It does not report experiments in Rs1 KO or Rho KO mice or a shift in transduction relative to wild-type mice; searches for those models and the comparison found no supporting passage. (LLM, conf=0.88)
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“Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1KO and RhoKO mice (XLRS and RP models, respectively) compared to wild-type mice [310,311].”
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Authors: Giove, T. J., Sena-Esteves, M., & Eldred, W. D.
Affiliations: Boston University (US)
Venue: Experimental Eye Research
Publisher: Elsevier BV
Published: 2010-11
Volume: 91
Issue: 5
Pages: 652-659
ISSN: 0014-4835 (ISSN-L)
DOI: 10.1016/j.exer.2010.08.011
PMC: PMC2962726
OpenAlex: W2074694316
Cited by: 27
References: 41
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 3 · 2013: 1 · 2012: 1
FWCI: 0.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Eye Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Eye Institute (R01EY004785, EY004758)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: adeno-associated virus, AAVrh10, AAV serotypes, inner retina, intravitreal injection, retinal gene delivery, ganglion cell layer, inner nuclear layer, amacrine cells, horizontal cells, Müller cells, bipolar cells, glial fibrillary acidic protein, transduction efficiency, cell tropism
MeSH terms: Dependovirus, Animals, Genetic Vectors, Glial Fibrillary Acidic Protein, Injections, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Retina, Transduction, Genetic, Vitreous Body, Fluorescent Antibody Technique, Indirect, Green Fluorescent Proteins, Mice, Viral Tropism

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Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection

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