The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation

Kim, Jin Hyoung; Kim, Myung Hun; Jo, Dong Hyun; Yu, Young Suk; Lee, Tae Geol; Kim, Jeong Hun

doi:10.1016/j.biomaterials.2010.11.030

Cited by 149 publications

(116 citation statements)

References 43 publications

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“…12 Furthermore, AuNPs are also reported to suppress VEGFR-2 activation. 13 Gold nanoparticles have been explored with respect to their efficacy in the treatment of various angiogenesis-related diseases and have been used to suppress progression in various tumor models and in a retinopathy of a prematurity animal model. 13,14 Therefore, in the present study, the antiangiogenic effects and molecular mechanisms of AuNPs on VEGF-induced angiogenesis were investigated.…”

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confidence: 99%

“…13 Gold nanoparticles have been explored with respect to their efficacy in the treatment of various angiogenesis-related diseases and have been used to suppress progression in various tumor models and in a retinopathy of a prematurity animal model. 13,14 Therefore, in the present study, the antiangiogenic effects and molecular mechanisms of AuNPs on VEGF-induced angiogenesis were investigated. Moreover, the angiogenic effects of AuNPs in an experimental CNV model were evaluated to determine their potential as a treatment for CNV developing secondary to neovascular AMD.…”

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confidence: 99%

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The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

Roh

Rho

Cho

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice.METHODS. Choroidal neovascularization was induced by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4. The effects of AuNPs on endothelial cell tube formation, proliferation, and cytotoxicity were evaluated using human umbilical vein endothelial cells (HUVECs) or human RPE cells. The activity of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and focal adhesion kinase (FAK) signaling pathways was also analyzed. RESULTS.The AuNPs reduced the extent of CNV. Mice treated with intravitreal AuNPs injections exhibited a 67.9% reduction in the extent of CNV lesions compared with the control group (P < 0.001). The size of the isolectin B4-labeled area was also significantly smaller in AuNP-treated groups compared with the control group (P < 0.001). Gold nanoparticles decreased vascular endothelial growth factor-induced HUVEC tube formation and proliferation but showed no RPE cell toxicity with the treatment doses administered. The phosphorylation of ERK1/2, Akt, and FAK in HUVECs was suppressed by AuNPs. CONCLUSIONS.Gold nanoparticles can inhibit laser-induced CNV in mice and may have an indication for the treatment of CNV.

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The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

Roh

Rho

Cho

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…During our efforts on developing anti-angiogenic drugs, [11][12][13][14][15] we recently extracted luteolin as a potent candidate from Platycodon grandiflorum, which is widely used in Asian traditional herbal medicine. 16 Luteolin is a natural flavonoid, which can provide both short and long term anti-oxidative effect by directly neutralize toxic ROS by donating hydrogen ions and also modulate cell-signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Anti-Angiogenic Effect of Luteolin on Retinal Neovascularization via Blockade of Reactive Oxygen Species Production

Park

Cho

Jun

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Oxidative stress-induced vascular endothelial growth factor (VEGF) is thought to play a critical role in the pathogenesis of retinopathy of prematurity (ROP). This study was performed to investigate the anti-angiogenic effect of luteolin against reactive oxygen species (ROS)-induced retinal neovascularization.METHODS. The toxicity of luteolin was evaluated through modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human retinal microvascular endothelial cells (HRMECs) as well as TUNEL staining in the retina of C57BL/6J mice. After intravitreal injection of luteolin in the mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting. Anti-angiogenic activity of luteolin was evaluated by VEGF-induced migration and tube formation assay. The effect of luteolin on tertiarybutylhydroperoxide (t-BH)-induced ROS production was measured with 2 0 7 0 -dichlorofluorescein diacetate. The effect of luteolin on t-BH-induced and hypoxia-induced VEGF transcription and expression were evaluated by RT-PCR and Western blot, respectively. RESULTS.Luteolin never affected the viability of HRMECs up to 10 lM, where luteolin never induced any structural change in all retinal layers. Luteolin inhibited retinal neovascularization in the mouse model of ROP. Moreover, VEGF-induced migration and tube formation were significantly decreased by cotreatment of luteolin. Luteolin attenuated VEGF transcription via blockade of t-BH-induced ROS production. Luteolin suppressed hypoxia-induced VEGF expression via attenuating hypoxia inducible factor 1 a expression. CONCLUSIONS.Our results suggest that luteolin could be a potent anti-angiogenic agent for retinal neovascularization, which is related to anti-oxidative activity to block ROS production and to subsequently suppress VEGF expression and the proangiogenic effect of VEGF. (Invest Ophthalmol Vis Sci. 2012; 53:7718-7726)

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“…Targeting VEGFR-2 with decursin inhibits second messenger signaling in retinal cells (Kim et al, 2009a). The antiangiogenic effects of decursin have been largely attributed to reduced VEGFR-2 expression in endothelial cells.…”

Section: Decursinmentioning

confidence: 99%

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

Szabadfi

Pintér

Reglődi

et al. 2014

International Review of Cell and Molecular Biology

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The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation

Cited by 149 publications

References 43 publications

The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

Anti-Angiogenic Effect of Luteolin on Retinal Neovascularization via Blockade of Reactive Oxygen Species Production

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

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