Dataset Information

Essential Contribution of Macrophage Tie2 Signalling in a Murine Model of Laser-Induced Choroidal Neovascularization.

ABSTRACT: Wet age-related macular degeneration (AMD), which can cause progressive blindness, is characterised by choroid neovascularization (CNV) in the macular area. Although close attention has been paid to AMD, and anti-vascular endothelial growth factor (VEGF) drugs are available, its complex pathogenesis is still elusive. Tie2-expressing macrophages (TEMs) have been found to promote angiogenesis in remodel tissues and tumours. This study aimed to elucidate the role of macrophage Tie2 signalling in laser-induced CNV (LCNV). We observed that TEMs were responsible for the severity of CNV. Mechanistically, TEM deletion resulted in impaired LCNV due to the suppression of inflammatory angiogenesis and the promotion of apoptosis. We also observed that TEMs prevented apoptosis of b.End3 cells, but promoted their migration, proliferation and tube formation via VEGF, extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene (AKT)-dependent signalling pathways. The flow cytometry results comparing dry AMD patients and healthy controls with wet AMD patients showed that the percentage of Tie2⁺CD14⁺ cells was higher in the wet AMD patients' peripheral blood. This study demonstrates that Tie2 expression by macrophages intensifies CNV in LCNV murine models, thereby proposing an additional intervention option to inhibit CNV.

SUBMITTER: Yin X

PROVIDER: S-EPMC7295776 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Essential Contribution of Macrophage Tie2 Signalling in a Murine Model of Laser-Induced Choroidal Neovascularization.

Yin Xue X Zhang Bingyu B Chen Lei L Xia Wei W Liu Gaoqin G Zhu Xuefei X Ren Chi C Liu Weiming W Lu Peirong P

Scientific reports 20200615 1

Wet age-related macular degeneration (AMD), which can cause progressive blindness, is characterised by choroid neovascularization (CNV) in the macular area. Although close attention has been paid to AMD, and anti-vascular endothelial growth factor (VEGF) drugs are available, its complex pathogenesis is still elusive. Tie2-expressing macrophages (TEMs) have been found to promote angiogenesis in remodel tissues and tumours. This study aimed to elucidate the role of macrophage Tie2 signalling in la ...[more]

PMID: 32541815

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Project description:Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.

Dataset Information

Essential Contribution of Macrophage Tie2 Signalling in a Murine Model of Laser-Induced Choroidal Neovascularization.

Publications

Essential Contribution of Macrophage Tie2 Signalling in a Murine Model of Laser-Induced Choroidal Neovascularization.

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