ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Gene therapy with the caspase activation and recruitment domain reduces the ocular inflammatory response.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?Expert reviews in molecular medicine · 2024Review
- Gene Delivery of a Caspase Activation and Recruitment Domain Improves Retinal Pigment Epithelial Function and Modulates Inflammation in a Mouse Model with Features of Dry Age-Related Macular Degeneration.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2022Article
- Therapeutic Applications of Adeno-Associated Virus (AAV) Gene Transfer of HLA-G in the Eye.International journal of molecular sciences · 2022Review
- Regulated Tristetraprolin Overexpression Dampens the Development and Pathogenesis of Experimental Autoimmune Uveitis.Frontiers in immunology · 2020Article
- AAV Mediated Delivery of Myxoma Virus M013 Gene Protects the Retina against Autoimmune Uveitis.Journal of clinical medicine · 2019Article
- Expression of a CARD Slows the Retinal Degeneration of a Geographic Atrophy Mouse Model.Molecular therapy. Methods & clinical development · 2019Article
- Prospective Application of Activity-Based Proteomic Profiling in Vision Research-Potential Unique Insights into Ocular Protease Biology and Pathology.International journal of molecular sciences · 2019Review
- A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Modulation of three key innate immune pathways for the most common retinal degenerative diseases.EMBO molecular medicine · 2018Review
- Use of Laplacian Heat Diffusion Algorithm to Infer Novel Genes With Functions Related to Uveitis.Frontiers in genetics · 2018Article
- Inflammation and its role in age-related macular degeneration.Cellular and molecular life sciences : CMLS · 2016Review
- Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model.Disease models & mechanisms · 2016Article
- Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide.Investigative ophthalmology & visual science · 2016Article
- Management of noninfectious posterior uveitis with intravitreal drug therapy.Clinical ophthalmology (Auckland, N.Z.) · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammation is a key component of chronic and acute diseases of the eye. Our goal is to test anti-inflammatory genes delivered by an adeno-associated virus (AAV) vector as potential treatments for retinal inflammation. We developed a secretable and cell penetrating form of the caspase activation and recruitment domain (CARD) from the apoptosis-associated speck-like protein containing a CARD (ASC) gene that binds caspase-1 and inhibits its activation by the inflammasome. The secretion and cell penetration characteristics of this construct were validated in vitro by measuring its effects on inflammasome signaling in a monocyte cell line and in an retinal pigmented epithelium (RPE) cell line. This vector was then packaged as AAV particles and tested in the endotoxin-induced uveitis mouse model. Gene expression was monitored one month after vector injection by fluorescence fundoscopy. Ocular inflammation was then induced by injecting lipopolysaccharide into the vitreous and was followed by enucleation 24 hours later. Eyes injected with the secretable and cell penetrating CARD AAV vector had both a significantly lower concentration of IL-1β as well as a 64% reduction in infiltrating cells detected in histological sections. These results suggest that anti-inflammatory genes such as the CARD could be used to treat recurring inflammatory diseases like uveitis or chronic subacute inflammations of the eye.
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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 Socratic graph.