ArticleJCI insight2022
ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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, 16 citations in OpenAlex.
- Angiopoietin-Like 4 Induces Upregulation of VEGF and sVCAM1 Through JNK/c-Jun and JAK2/STAT5 Signaling Pathways.Investigative ophthalmology & visual science · 2026Article
- An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.Investigative ophthalmology & visual science · 2026Article
- Sustained-release CGRP microspheres accelerate diabetic wound healing by synergistically promoting neurovascular regeneration through modulation of macrophage and endothelial cell functions.Materials today. Bio · 2026Article
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- PM2.5 exposure induces transcriptomic changes in ARPE-19 cells with activation of TGFβ-mediated signaling pathways: A next-generation sequencing approach.Journal of the Chinese Medical Association : JCMA · 2025Article
- ANGPTL4: A Comprehensive Review of 25 Years of Research.Cancers · 2025Review
- ANGPTL4 promotes choroidal neovascularization and subretinal fibrosis through the endothelial‒mesenchymal transition.International ophthalmology · 2024Article
- VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.The Journal of clinical investigation · 2023Article
- Vitamin A deficiency compromises the barrier function of the retinal pigment epithelium.PNAS nexus · 2023Article
- Aflibercept more effectively weans patients with neovascular age-related macular degeneration off therapy compared with bevacizumab.The Journal of clinical investigation · 2023Article
- Primary tumor-derived systemic nANGPTL4 inhibits metastasis.The Journal of experimental medicine · 2023Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 3 countries.
Funding
Abstract
Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.
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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.