ArticleJCI insight2018
Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
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- The Early Pathogenesis of Diabetic Retinopathy and Its Attenuation by Sodium-Glucose Transporter 2 Inhibitors.Diabetes · 2024Article
- Role of macrophage in ocular neovascularization.Heliyon · 2024Review
- ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.International journal of molecular sciences · 2023Article
- Macrophage/microglia polarization for the treatment of diabetic retinopathy.Frontiers in endocrinology · 2023Review
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- Intestinal epithelial BLT1 promotes mucosal repair.JCI insight · 2022Article
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- LTB4 Promotes Acute Lung Injury via Upregulating the PLCDisease markers · 2022Article
- Identification of Potential Key Biomarkers and Immune Infiltration in Oral Lichen Planus.Disease markers · 2022Article
- Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities.Progress in retinal and eye research · 2021Review
- Review
- Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells.Scientific reports · 2020Article
- Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Betalain exerts a protective effect against glaucoma is majorly through the association of inflammatory cytokines.AMB Express · 2020Article
- The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders.International journal of molecular sciences · 2019Review
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is associated with aging and is a leading cause of blindness worldwide. Here, we demonstrate that leukotriene B4 (LTB4) receptor 1 (BLT1) promotes laser-induced choroidal neovascularization (CNV) in a mouse model for wet-type AMD. CNV was significantly less in BLT1-deficient (BLT1-KO) mice compared with BLT1-WT controls. Expression of several proangiogenic and profibrotic factors was lower in BLT1-KO eyes than in BLT1-WT eyes. LTB4 production in the eyes was substantially increased in the early phase after laser injury. BLT1 was highly expressed in M2 macrophages in vitro and in vivo, and ocular BLT1+ M2 macrophages were increased in the aged eyes after laser injury. Furthermore, M2 macrophages were rapidly attracted by LTB4 and subsequently produced VEGF-A- through BLT1-mediated signaling. Consequently, intravitreal injection of M2 macrophages augmented CNV formation, which was attenuated by BLT1 deficiency. Thus, laser-induced injury to the retina triggered LTB4 production and attracted M2 macrophages via BLT1, leading to development of CNV. A selective BLT1 antagonist (CP105696) and 3 LTB4 inhibitors (zileuton, MK-886, and bestatin) reduced CNV in a dose-dependent manner. CP105696 also inhibited the accumulation of BLT1+ M2 macrophages in the laser-injured eyes of aged mice. Together, these results indicate that the LTB4-BLT1 axis is a potentially novel therapeutic target for CNV of wet-type AMD.
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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.