ArticleHuman gene therapy2021
Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes.
Article in Human gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Retinal Layer Changes With Aging and Cognitive Decline in Rhesus Macaques.Translational vision science & technology · 2026Article
- Storage and Stability of AAV-Containing Fibrin Hydrogels for Retinal Gene Therapy.Gels (Basel, Switzerland) · 2026Article
- Gene therapy induces pigmentation in induced pluripotent stem cell-derived retinal pigment epithelium of OCA1A patients and albino rat eye.Molecular therapy. Advances · 2026Article
- 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
- Bibliometric and visualized analysis of the therapeutic application of suprachoroidal space from 2000 to 2024.International journal of surgery (London, England) · 2026Article
- Surgical Approaches to Retinal Gene Therapy: 2025 Update.Bioengineering (Basel, Switzerland) · 2025Review
- A Comprehensive Review of Clinically Applied Adeno-Associated Virus-Based Gene Therapies for Ocular Disease.Human gene therapy · 2025Review
- Retinal gene therapy using epiretinal AAV-containing fibrin hydrogel implants.Science advances · 2025Article
- Suprachoroidal Delivery of Viral and Nonviral Vectors for Treatment of Retinal and Choroidal Vascular Diseases.American journal of ophthalmology · 2025Review
- Safety and efficacy of CRISPR-mediated genome ablation of VEGFA as a treatment for choroidal neovascularization in nonhuman primate eyes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Adeno-Associated Virus Vectors in Retinal Gene Therapy: Challenges, Innovations, and Future Directions.Biomolecules · 2025Review
- Gene Therapy in Diabetic Retinopathy and Diabetic Macular Edema: An Update.Journal of clinical medicine · 2025Review
- 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
- Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions.The Yale journal of biology and medicine · 2024Review
- What's New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023.Pharmaceuticals (Basel, Switzerland) · 2024Review
- An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.Nature communications · 2024Article
- Next generation therapeutics for retinal neurodegenerative diseases.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Progress in the Application of Microneedles in Eye Disorders and the Proposal of the Upgraded Microneedle with Spinule.Pharmaceutical research · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The suprachoroid is a potential space located between the sclera and choroid of the eye, which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of adeno-associated virus (AAV)8 using transscleral microneedles enables widespread transgene expression in eyes of nonhuman primates, but may cause intraocular inflammation. We characterized the host humoral and cellular immune responses after suprachoroidal delivery of AAV8 expressing green fluorescent protein (GFP) in rhesus macaques, and found that it can induce mild chorioretinitis that resolves after systemic corticosteroid administration, with recovery of photoreceptor morphology, but persistent immune cell infiltration after 3 months, corresponding to a loss of GFP expression from retinal pigment epithelial cells, but persistent expression in scleral fibroblasts. Suprachoroidal AAV8 triggered B cell and T cell responses against GFP, but only mild antibody responses to the viral capsid compared to intravitreal injections of the same vector and dose. Systemic biodistribution studies showed lower AAV8 levels in liver and spleen after suprachoroidal injection compared with intravitreal delivery. Our findings suggest that suprachoroidal AAV8 primarily triggers host immune responses to GFP, likely due to sustained transgene expression in scleral fibroblasts outside the blood-retinal barrier, but elicits less humoral immune reactivity to the viral capsid than intravitreal delivery due to lower egress into systemic circulation. As GFP is not native to primates and not a clinically relevant transgene, suprachoroidal AAV delivery of human transgenes may have significant translational potential for retinal gene therapy.
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What OpenQuestion holds
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.