ArticleGene therapy2021
Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1.
Article in Gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Frontiers of optic nerve regeneration research: an analysis of the top 100 most influential articles in the field from 2005 to 2025.Frontiers in neuroscience · 2025Pooled it
- The Role of Nrf2 in SIRT1-Mediated RGC Neuroprotection in Traumatic Optic Neuropathy.Translational vision science & technology · 2026Article
- The 5-HT1A receptor antagonist WAY-100635 maleate promotes retinal ganglion cell differentiation and protects the retino-visual circuits.Communications medicine · 2026Article
- A Mini-Review on Gene Therapy in Glaucoma and Future Directions.International journal of molecular sciences · 2024Review
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- AAV-NDI1 Therapy Provides Significant Benefit to Murine and Cellular Models of Glaucoma.International journal of molecular sciences · 2024Article
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- Comparison of SNCG and NEFH Promoter-Driven Expression of Human SIRT1 Expression in a Mouse Model of Glaucoma.Translational vision science & technology · 2024Article
- CX3CL1-CX3CR1 axis protects retinal ganglion cells by inhibiting microglia activation in a distal optic nerve trauma model.Inflammation and regeneration · 2024Article
- Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- AAV2 vector optimization for retinal ganglion cell-targeted delivery of therapeutic genes.Gene therapy · 2024Article
- Retinal ganglion cell type-specific expression of synuclein family members revealed by scRNA-sequencing.International journal of medical sciences · 2024Article
- Mesenchymal stem cells for repairing glaucomatous optic nerve.International journal of ophthalmology · 2024Review
- Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.Inflammation and regeneration · 2023Article
- Cell-Specific Expression of Human SIRT1 by Gene Therapy Reduces Retinal Ganglion Cell Loss Induced by Elevated Intraocular Pressure.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Long Non-Coding RNAs in Retinal Ganglion Cell Apoptosis.Cellular and molecular neurobiology · 2023Review
- Repeat Brn3a immunolabeling rescues faded staining and improves detection of retinal ganglion cells.Experimental eye research · 2023Article
- Article
- Peptains block retinal ganglion cell death in animal models of ocular hypertension: implications for neuroprotection in glaucoma.Cell death & disease · 2022Article
- An Altered Neurovascular System in Aging-Related Eye Diseases.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
SIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism of loss is not known, prior evidence suggests this is through oxidative stress to either neighboring cells or RGC specifically. We investigated the neuroprotective potential of RGC-selective SIRT1 gene therapy in the optic nerve crush (ONC) model. We hypothesized that AAV-mediated overexpression of SIRT1 in RGCs reduces RGC loss, thereby preserving visual function. Cohorts of C57Bl/6J mice received intravitreal injection of experimental or control AAVs using either a ganglion cell promoter or a constitutive promoter and ONC was performed. Visual function was examined by optokinetic response (OKR) for 7 days following ONC. Retina and optic nerves were harvested to investigate RGC survival by immunolabeling. The AAV7m8-SNCG.SIRT1 vector showed 44% transduction efficiency for RGCs compared with 25% (P > 0.05) by AAV2-CAG.SIRT1, and AAV7m8-SNCG.SIRT1 drives expression selectively in RGCs in vivo. Animals modeling ONC demonstrated reduced visual acuity compared to controls. Intravitreal delivery of AAV7m8-SNCG.SIRT1 mediated significant preservation of the OKR and RGC survival compared to AAV7m8-SNCG.eGFP controls, an effect not seen with the AAV2 vector. RGC-selective expression of SIRT1 offers a targeted therapy for an animal model with significant ganglion cell loss. Over-expression of SIRT1 through AAV-mediated gene transduction suggests a RGC selective component of neuro-protection using the ONC model. This study expands our understanding of SIRT1 mediated neuroprotection in the context of compressive or traumatic optic neuropathy, making it a strong therapeutic candidate for testing in all optic neuropathies.
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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.