ArticleInvestigative ophthalmology & visual science2018
SIRT1 and NRF2 Gene Transfer Mediate Distinct Neuroprotective Effects Upon Retinal Ganglion Cell Survival and Function in Experimental Optic Neuritis.
Article in Investigative ophthalmology & visual science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- The Role of Nrf2 in SIRT1-Mediated RGC Neuroprotection in Traumatic Optic Neuropathy.Translational vision science & technology · 2026Article
- The aging eye: navigating molecular mechanisms and innovative interventions.Biogerontology · 2026Review
- Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges.Molecules (Basel, Switzerland) · 2025Review
- SIRT1-based therapy targets a gene program involved in mitochondrial turnover in a model of retinal neurodegeneration.Scientific reports · 2025Article
- Targeted Neuroprotection of Retinal Ganglion Cells Via AAV2-hSyn-NGF Gene Therapy in Glaucoma Models.Investigative ophthalmology & visual science · 2025Article
- Sirtuin1 mitigates hypoxia-induced cardiomyocyte apoptosis in myocardial infarction via PHD3/HIF-1α.Molecular medicine (Cambridge, Mass.) · 2025Article
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- AAV2 vector optimization for retinal ganglion cell-targeted delivery of therapeutic genes.Gene therapy · 2024Article
- Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injuryInternational journal of ophthalmology · 2024Article
- Review
- Nanoparticles Enhance Solubility and Neuroprotective Effects of Resveratrol in Demyelinating Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 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
- The role of SIRT1 level and SIRT1 gene polymorphisms in optic neuritis patients with multiple sclerosis.Orphanet journal of rare diseases · 2023Article
- Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.Frontiers in immunology · 2023Article
- Article
- Article
- Role of Sirtuins in Physiology and Diseases of the Central Nervous System.Biomedicines · 2022Review
- Article
- Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- SARM1 Ablation Is Protective and Preserves Spatial Vision in an In Vivo Mouse Model of Retinal Ganglion Cell Degeneration.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Optic neuritis is a condition defined by autoimmune-mediated demyelination of the optic nerve and death of retinal ganglion cells. SIRT1 and NRF2 stimulate anti-inflammatory mechanisms and have previously demonstrated therapeutic value in preclinical models of neurodegenerative disease. Here we investigated the neuroprotective potential of SIRT1 or NRF2 gene transfer using adeno-associated virus (AAV) vectors in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Methods: C57Bl/6J mice were administered intravitreal doses of AAV2 vectors and immunized to induce EAE symptoms. Visual function was examined by recording the optokinetic response (OKR) just prior to EAE induction and once every 7 days postinduction for 7 weeks. Retina and optic nerves were harvested to investigate retinal ganglion cell survival (immunolabeling with Brn3a antibodies); inflammation (hematoxylin and eosin staining); and demyelination (luxol fast blue staining). Results: Animals modeling EAE demonstrate reduced visual acuity compared to sham-induced controls. Intravitreal delivery of AAV2-NRF2 did not preserve visual function. However, AAV2-SIRT1 mediated significant preservation of the OKR compared to AAV2-eGFP controls. Treatment with AAV2-NRF2 promoted RGC survival while AAV2-SIRT1 mediated an upward trend in protection compared to vehicle and AAV2-eGFP controls. Neither NRF2 nor SIRT1 gene augmentation was able to suppress optic nerve inflammation or demyelination. Conclusions: AAV-mediated overexpression of NRF2 or SIRT1 within RGCs mediates distinct neuroprotective effects upon visual function and RGC survival. This study expands our understanding of SIRT1 and NRF2-mediated neuroprotection in the context of MS pathogenesis and 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.