ArticleJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics2012
Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal neovascularization.
Article in Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Novel evidence for complement system activation in chick myopia and hyperopia models: a meta-analysis of transcriptome datasets.Scientific reports · 2017Pooled it
- Alkylglycerols reduce serum complement and plasma vascular endothelial growth factor in obese individuals.Inflammopharmacology · 2016Trial
- Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice.World journal of hepatology · 2024Article
- Regulatable Complement Inhibition of the Alternative Pathway Mitigates Wet Age-Related Macular Degeneration Pathology in a Mouse Model.Translational vision science & technology · 2023Article
- Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.Immunological reviews · 2023Review
- Novel approach to antiangiogenic factors in age-related macular degeneration therapy.Central-European journal of immunology · 2022Review
- Natural immunoglobulin M-based delivery of a complement alternative pathway inhibitor in mouse models of retinal degeneration.Experimental eye research · 2021Article
- Mechanisms of FH Protection Against Neovascular AMD.Frontiers in immunology · 2020Article
- The use of Matrigel combined with encapsulated cell technology to deliver a complement inhibitor in a mouse model of choroidal neovascularization.Molecular vision · 2020Article
- Delivery of CR2-fH Using AAV Vector Therapy as Treatment Strategy in the Mouse Model of Choroidal Neovascularization.Molecular therapy. Methods & clinical development · 2018Article
- Encapsulated Cell Technology-Based Delivery of a Complement Inhibitor Reduces Choroidal Neovascularization in a Mouse Model.Translational vision science & technology · 2018Article
- Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation.Molecular vision · 2018Article
- Complement factor H in AMD: Bridging genetic associations and pathobiology.Progress in retinal and eye research · 2018Review
- New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities.Seminars in immunology · 2016Review
- Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy.Journal of the American Society of Nephrology : JASN · 2016Article
- C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells.BioMed research international · 2016Article
- Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.Drug design, development and therapy · 2016Article
- Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo.Investigative ophthalmology & visual science · 2015Article
- Intravitreal inhibition of complement C5a reduces choroidal neovascularization in mice.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2015Article
- Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.Progress in retinal and eye research · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGenetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD.
methodsChoroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined.
resultsCNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid.
conclusionSystemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.
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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.