ArticleThe Journal of clinical investigation2017
VEGF regulates local inhibitory complement proteins in the eye and kidney.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.
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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
93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review.Blood cancer journal · 2024Pooled it
- Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Pooled it
- Bibliometric analysis and visualization of inflammation in the field of diabetic retinopathy research (2006-2025).Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Renal toxicity during VEGF-pathway inhibition in cancer: a practical review of proteinuria, hypertension, and kidney-limited thrombotic microangiopathy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Two cases of proteasome inhibitors related thrombotic microangiopathies and literature review.Thrombosis journal · 2026Article
- Data-Driven Stratification Reveals 3 Distinct Clinicopathologic Phenotypes in Renal Thrombotic Microangiopathy.Mayo Clinic proceedings. Digital health · 2026Article
- Tissue-resident macrophages maintain choroidal homeostasis by complement dependent and independent mechanisms.Journal of neuroinflammation · 2026Article
- Lenvatinib-associated hyaline occlusive glomerular microangiopathy.Clinical kidney journal · 2026Article
- Renal-Limited Thrombotic Microangiopathy due to Anti-VEGF/TKI Immunotherapy for Metastatic Renal Cell Carcinoma Presenting as Nephrotic Syndrome: A Case Report and Literature Review.Clinical case reports · 2026Article
- Rapid Recognition of Carfilzomib-Induced Thrombotic Microangiopathy and Early Application of Eculizumab Successfully Rescued Two Relapsed Myeloma Patients.Chronic diseases and translational medicine · 2026Article
- Biopsy-proven tyrosine kinase inhibitor-associated renal injury: a case series.Clinical kidney journal · 2026Article
- Anticancer drug-induced nephrotoxicity: biopsy-proven patterns and outcomes across chemotherapy, targeted therapy, and immune checkpoint inhibitors.Renal failure · 2025Article
- Bevacizumab-associated glomerular microangiopathy: a case report and literature review.BMC nephrology · 2025Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.Experimental eye research · 2025Review
- Post-transplant Thrombotic Microangiopathy.Journal of the American Society of Nephrology : JASN · 2025Review
- Incidence, Characteristics, and Outcomes of Macular Neovascularization in Extensive Macular Atrophy with Pseudodrusen-like Appearance.Retina (Philadelphia, Pa.) · 2025Article
- Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.Stem cell reports · 2025Article
- Complement Factor H Promotes the Growth of Lung Adenocarcinoma Cells through the JAK2/STAT3 Signaling Pathway.Current cancer drug targets · 2025Article
- Dynamic Complement Protein Changes in Aqueous Humor and Plasma of Patients With Retinal Vein Occlusion During Ranibizumab Treatment.Journal of inflammation research · 2025Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF inhibition could reduce cellular complement regulatory capacity. VEGF antagonism also increased markers of endothelial cell activation, which was partially reduced by genetic complement inhibition. Together, these results suggest that VEGF protects the retinal and glomerular microvasculature, not only through VEGFR2-mediated vasculotrophism, but also through modulation of local complement proteins that could protect against complement-mediated damage. Though further study is warranted, these findings could be relevant for patients receiving VEGF antagonists.
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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.