ArticleGene therapy2011
Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration.
Article in Gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway.Immunological reviews · 2023Review
- Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Nitrite Modification of Extracellular Matrix Alters CD46 Expression and VEGF Release in Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2015Article
- Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration.Investigative ophthalmology & visual science · 2015Article
- Highly efficient retinal gene delivery with helper-dependent adenoviral vectors.Genes & diseases · 2014Article
- Retinal pigment epithelial cell death by the alternative complement cascade: role of membrane regulatory proteins, calcium, PKC, and oxidative stress.Investigative ophthalmology & visual science · 2014Article
- Mechanism of inflammation in age-related macular degeneration.Mediators of inflammation · 2012Review
- Soluble CD59 expressed from an adenovirus in vivo is a potent inhibitor of complement deposition on murine liver vascular endothelium.PloS one · 2011Article
- Adeno-associated virus mediated delivery of an engineered protein that combines the complement inhibitory properties of CD46, CD55 and CD59.The journal of gene medicineArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the alternative pathway of the complement system has been implicated in the pathogenesis of age-related macular degeneration. Membrane attack complex (MAC) has been identified mainly on the Bruch's membrane and drusen underlying the retinal pigment epithelium (RPE). Membrane cofactor protein (CD46) preferentially regulates the alternative pathway of complement. The aim of this study was to evaluate the potential of increasing CD46 expression on RPE cells using an adenovirus as a gene therapy approach to reduce alternative pathway-mediated damage to RPE cells. We generated a recombinant adenovirus vector expressing human CD46 (hCD46) and delivered the vector to murine hepatocytes and RPE cells in vitro. After incubation in human serum in conditions in which the classical pathway of complement was blocked, we measured alternative pathway-mediated damage of these cells by quantifying lysis and MAC formation. Adenovirus expressing hCD46 was delivered to the subretinal space of adult mice, and 1 week later, ocular flat mounts were challenged with human serum and the levels of complement-mediated damage was quantified. Adenovirus-mediated delivery of hCD46 localizes to the basal and lateral surfaces of RPE cells where it offers protection from alternative pathway-mediated damage, but not classical, allowing the classical pathway to function unhindered.
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