ArticleThe Journal of clinical investigation2015
Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
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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
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 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
- [Gene therapy as a treatment concept for inherited retinal diseases].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2015Pooled 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
- Article
- Modulation of Systemic Osmolarity Alters Retinal Thickness and Schisis Cavities Without Blood Retinal Barrier Disruption in Rs1 Knockout Mice.Investigative ophthalmology & visual science · 2026Article
- Multimodal imaging of stellate nonhereditary idiopathic foveomacular retinoschisis with midperipheral retinoschisis and microvasculopathy.American journal of ophthalmology case reports · 2026Article
- Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium.Scientific reports · 2026Article
- Investigating the Role of Zebrafish Retinoschisin Homologs Rs1a and Rs1b During Retinal Development.Developmental neurobiology · 2026Article
- A mechanism for pathological oscillations in mouse retinal ganglion cells in a model of night blindness.The Journal of general physiology · 2025Article
- A genome-wide investigation of insidious uveitis in Appaloosa horses.BMC genomics · 2025Article
- Immune landscape in children with X-linked retinoschisis.BMC immunology · 2025Article
- 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
- Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.Investigative ophthalmology & visual science · 2025Article
- Understanding the phenotype of genetically associated electronegative ERG retinopathies: comparing the full-field ERG b:a ratio.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- A Novel AAV Capsid-Mediated RS1 Gene Therapy Restored Retinal Function to Wild-Type Levels in Rs1R213W Mouse Model.Investigative ophthalmology & visual science · 2025Article
- Advancing Insights into Pediatric Macular Diseases: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Proteomic Analysis of Retinas in a Rat Model of High-Fat Diet-Induced Type 2 Diabetes: Implications of Interventional Targets for Nonproliferative Diabetic Retinopathy.Drug design, development and therapy · 2025Article
- 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
- Article
- Gene Therapies in Clinical Development to Treat Retinal Disorders.Molecular diagnosis & therapy · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology.
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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.