ArticleHuman gene therapy2016
Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal Structure and Function.
Article in Human gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- The Road towards Gene Therapy for X-Linked Juvenile Retinoschisis: A Systematic Review of Preclinical Gene Therapy in Cell-Based and Rodent Models of XLRS.International journal of molecular sciences · 2024Pooled it
- Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Trial
- Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium.Scientific reports · 2026Article
- Synthesis and characterization of an injectable telechelic material for the epiretinal delivery of retinal gene therapies.Journal of materials chemistry. B · 2026Article
- Investigating the Role of Zebrafish Retinoschisin Homologs Rs1a and Rs1b During Retinal Development.Developmental neurobiology · 2026Article
- A Comprehensive Review of Clinically Applied Adeno-Associated Virus-Based Gene Therapies for Ocular Disease.Human gene therapy · 2025Review
- Intravitreal adenine base editing of RS1 improves vision in a preclinical mouse model of retinoschisis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025Review
- A Novel AAV Capsid-Mediated RS1 Gene Therapy Restored Retinal Function to Wild-Type Levels in Rs1R213W Mouse Model.Investigative ophthalmology & visual science · 2025Article
- Review
- Identifying Multiomic Signatures of X-Linked Retinoschisis-Derived Retinal Organoids and Mice Harboring Patient-Specific Mutation Using Spatiotemporal Single-Cell Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy.Stem cell research & therapy · 2024Article
- OCT Intensity of the Region between Outer Retina Band 2 and Band 3 as a Biomarker for Retinal Degeneration and Therapy.Bioengineering (Basel, Switzerland) · 2024Article
- Intravitreal injection of new adeno-associated viral vector: Enhancing retinoschisin 1 gene transduction in a mouse model of X-linked retinoschisis.Biochemistry and biophysics reports · 2024Article
- The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hFrontiers in medicine · 2024Article
- An osmolarity dependent mechanism partially ameliorates retinal cysts and rescues cone function in a mouse model of X-linked retinoschisis.Frontiers in medicine · 2024Article
- Diurnal functional and anatomical changes in X-linked retinoschisis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Article
- Translatability barriers between preclinical and clinical trials of AAV gene therapy in inherited retinal diseases.Vision research · 2023Review
- X-Linked Retinoschisis.Cold Spring Harbor perspectives in medicine · 2023Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Gene therapy for inherited retinal diseases has been shown to ameliorate functional and structural defects in both animal models and in human clinical trials. X-linked retinoschisis (XLRS) is an early-age onset macular dystrophy resulting from loss of an extracellular matrix protein (RS1). In preparation for a human clinical gene therapy trial, we conducted a dose-range efficacy study of the clinical vector, a self-complementary AAV delivering a human retinoschisin (RS1) gene under control of the RS1 promoter and an interphotoreceptor binding protein enhancer (AAV8-scRS/IRBPhRS), in the retinoschisin knockout (Rs1-KO) mouse. The therapeutic vector at 1 × 10(6) to 2.5 × 10(9) (1E6-2.5E9) vector genomes (vg)/eye or vehicle was administered to one eye of 229 male Rs1-KO mice by intravitreal injection at 22 ± 3 days postnatal age (PN). Analysis of retinal function (dark-adapted electroretinogram, ERG), structure (cavities and outer nuclear layer thickness) by in vivo retinal imaging using optical coherence tomography, and retinal immunohistochemistry (IHC) for RS1 was done 3-4 months and/or 6-9 months postinjection (PI). RS1 IHC staining was dose dependent across doses ≥1E7 vg/eye, and the threshold for significant improvement in all measures of retinal structure and function was 1E8 vg/eye. Higher doses, however, did not produce additional improvement. At all doses showing efficacy, RS1 staining in Rs1-KO mouse was less than that in wild-type mice. Improvement in the ERG and RS1 staining was unchanged or greater at 6-9 months than at 3-4 months PI. This study demonstrates that vitreal administration of AAV8 scRS/IRBPhRS produces significant improvement in retinal structure and function in the mouse model of XLRS over a vector dose range that can be extended to a human trial. It indicates that a fully normal level of RS1 expression is not necessary for a therapeutic effect.
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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.