ArticleInvestigative ophthalmology & visual science2017
β2-Adrenergic Receptor Antagonism Attenuates CNV Through Inhibition of VEGF and IL-6 Expression.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Beta-blockers improve neurological outcomes of cerebral cavernous malformations: a systematic review.Neurosurgical review · 2026Pooled it
- The effect of combination therapy with intravitreal bevacizumab and topical timolol-dorzolamide eye drops on diabetic macular edema: a double-blind randomized controlled trial.International ophthalmology · 2024Trial
- A Randomized Controlled Pilot Study: Combined 595-nm Pulsed Dye Laser Treatment and Oxymetazoline Hydrochloride Topical Cream Superior to Oxymetazoline Hydrochloride Cream for Erythematotelangiectatic Rosacea.Lasers in surgery and medicine · 2021Trial
- Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential.Frontiers in physiology · 2026Review
- Research progress on the use of beta-blockers in the progression prevention, and treatment of retinopathy of prematurity.Frontiers in pediatrics · 2026Review
- Bioadhesive Eudragit RLPharmaceutics · 2025Article
- Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- The Role of Radiosensitizing Drugs in Osteosarcoma Treatment: Mechanisms and Clinical Perspectives.Drug design, development and therapy · 2025Review
- Adrenoceptors in the Eye - Physiological and Pathophysiological Relevance.Handbook of experimental pharmacology · 2024Review
- The βAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Intravitreal bevacizumab plus propranolol for neovascular age-related macular degeneration (the BEVALOL study): a phase I clinical trial.International journal of retina and vitreous · 2023Article
- Overactivation of Norepinephrine-β2-Adrenergic Receptor Axis Promotes Corneal Neovascularization.Investigative ophthalmology & visual science · 2023Article
- β-Adrenoreceptors as Therapeutic Targets for Ocular Tumors and Other Eye Diseases-Historical Aspects and Nowadays Understanding.International journal of molecular sciences · 2023Review
- Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.Molecular vision · 2023Article
- Article
- Review: The Development of Risk Factors and Cytokines in Retinal Vein Occlusion.Frontiers in medicine · 2022Review
- Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis.Scientific reports · 2021Article
- Review
- Assessment of the safety of intravitreal injection of metoprolol tartrate in rabbits.Documenta ophthalmologica. Advances in ophthalmology · 2021Article
- Selective β2-Adrenoceptor Blockade Rescues Mandibular Growth Retardation in Adolescent Rats Exposed to Chronic Intermittent Hypoxia.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: The role of β-adrenergic receptor (AR) signaling in neovascular ocular diseases has recently emerged. We have previously reported that intraperitoneal propranolol inhibits choroidal neovascularization (CNV) in vivo and β2-AR blockade reduces vascular endothelial growth factor (VEGF) expression in mouse retinal pigment epithelium and choroidal endothelial cells in culture. Here we tested the hypothesis that the β2-AR regulates CNV through modulation of VEGF and inflammatory cytokine expression. Methods: Mice were subjected to laser burns, inducing CNV, and were treated with an intravitreal β2-AR antagonist. After 3 and 5 days, total eye interleukin-6 (IL-6) and VEGF protein levels were measured, respectively. After 14 days, CNV was measured on choroidal-scleral flatmounts. The effects of β-AR signaling on VEGF and IL-6 expression were investigated in various mouse retinal and human RPE cells by using specific β-AR agonists and antagonists. Results: β2-Adrenergic receptor signaling increased Vegf mRNA expression by approximately 3- to 4-fold in mouse retinal microglia and pericytes in culture. β2-Adrenergic receptor signaling upregulated IL-6 mRNA expression between 10- and 60-fold in mouse retinal microglia, pericytes, RPE, and choroidal endothelial cells in culture. Intravitreal injection of β2-AR antagonist ICI 118,551 reduced CNV by 35% and decreased IL-6 protein levels by approximately 50%. In primary human RPE cells, β2-AR activation also stimulated VEGF and IL-6 mRNA expression by 2- and 10-fold, respectively. Conclusions: Anti-VEGF therapy for CNV is highly effective; however, some patients are resistant to therapy while others undergo repeated, frequent treatments. β2-Adrenergic receptor signaling is a potential therapeutic target because of its angiogenic and inflammatory properties.
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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.