ArticleInvestigative ophthalmology & visual science2021
Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice.
Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Gene therapy strategies in ophthalmology-an overview of current developments and future prospects.Journal of applied genetics · 2026Review
- Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes.Ophthalmology science · 2026Article
- Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses.Frontiers in immunology · 2026Article
- Characterization of adeno-associated viral transduction of retinal ganglion cells in adult and old mice.Molecular therapy. Methods & clinical development · 2025Article
- Preclinical Study on the Long-Term Efficacy and Safety of Sustained-Release Gas6 Liposomes Combined With MERTK Gene Therapy for Retinitis Pigmentosa.Translational vision science & technology · 2025Article
- IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells.JCI insight · 2025Article
- Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes.Molecular therapy. Methods & clinical development · 2025Article
- Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Deciphering infectious uveitis etiology: Immune cell profiling in keratic precipitates using in vivo confocal microscopy.Heliyon · 2024Article
- The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2.Gene therapy · 2024Article
- Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.Investigative ophthalmology & visual science · 2024Article
- AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?Expert reviews in molecular medicine · 2024Review
- Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.Cold Spring Harbor perspectives in medicine · 2024Review
- Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice.International journal of ophthalmology · 2024Article
- Food and Drug Administration Guidance on Design of Clinical Trials for Gene Therapy Products with Potential for Genome Integration or Genome Editing and Associated Long-Term Follow-Up of Research Subjects.Applied biosafety : journal of the American Biological Safety Association · 2022Review
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Gene Therapy for Rhodopsin Mutations.Cold Spring Harbor perspectives in medicine · 2022Article
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Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: To characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy. Methods: AAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls. Results: Optical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8- T cells were the dominant CD45+ cell population in AAV injected eyes. Conclusions: Intravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.