ArticleInvestigative ophthalmology & visual science2016
Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The aging eye: navigating molecular mechanisms and innovative interventions.Biogerontology · 2026Review
- Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.International journal of molecular sciences · 2025Review
- Antioxidant Peptides Derived from Woody Oil Resources: Mechanisms of Redox Protection and Emerging Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Retinal Penetrating Adeno-Associated Virus.Investigative ophthalmology & visual science · 2024Article
- AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?Expert reviews in molecular medicine · 2024Review
- Optimizing the sodium iodate model: Effects of dose, gender, and age.Experimental eye research · 2024Article
- Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis.Frontiers in medicine · 2024Article
- Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.Neural regeneration research · 2023Review
- Drug-Repurposing Strategy for Dimethyl Fumarate.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Gene-agnostic approaches to treating inherited retinal degenerations.Frontiers in cell and developmental biology · 2023Review
- Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina.Molecular vision · 2023Article
- Establishment of High-Efficiency Screening System for Gene Deletion inJournal of fungi (Basel, Switzerland) · 2022Article
- Article
- Deletion ofFrontiers in cell and developmental biology · 2021Article
- Mitochondria: The Retina's Achilles' Heel in AMD.Advances in experimental medicine and biology · 2021Article
- Cell Penetrating Peptides, Novel Vectors for Gene Therapy.Pharmaceutics · 2020Review
- Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation.Molecular neurobiology · 2020Article
- Depletion of Mitochondrial DNA in Differentiated Retinal Pigment Epithelial Cells.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeOxidative stress has been linked to several ocular diseases, initiating an inflammatory response that increases tissue injury. The Nrf2 transcription factor regulates expression of antioxidant genes and is tightly regulated by Kelch-Like ECH-Associated Protein 1 (Keap-1). We evaluate the antioxidant and anti-inflammatory properties of an adeno-associated virus (AAV) vector delivering an Nrf2-derived peptide that binds Keap-1.
methodsThe sequence of the Nrf2 peptide was fused to a cell-penetrating peptide (Tat-peptide) sequence (TatNrf2mer). The effects of lentiviral-delivered TatNrf2mer were studied in vitro. Transcript (quantitative [q] RT-PCR) and protein levels (ELISA and immunofluorescence) were quantified. Cell viability was measured by MTT and Cell Titer assays. The AAV vectors were packaged with the TatNrf2mer fused to secretable green fluorescent protein (GFP) under the control of the small chicken β actin promoter. The protective effects of this vector were evaluated in a model of RPE oxidative injury and in a mouse model of uveitis after intravitreal injection.
resultsExpression of TatNrf2mer peptide induced antioxidant gene expression, blocked IL-1β secretion, and protected cells from oxidative injury. In mice, TatNrf2mer expression partially protected photoreceptor function based on ERG responses and optical coherence tomography measurements in the sodium iodate (NaIO3) model. Furthermore, sGFP-TatNrf2mer expression decreased IL-1β and IL-6 in the NaIO3-treated mice, and resulted in a 54% decrease in the number of inflammatory cells in the vitreous body of the endotoxin-induced uveitis mouse model.
conclusionsThe intravitreally delivered AAV-TatNrf2mer has antioxidant and anti-inflammatory effects in widely-used models of ocular injury, suggesting it also could be useful in ocular diseases associated with oxidative stress and inflammasome activation.
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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.