Intravitreal Tanibirumab, a Fully Human Monoclonal Antibody Against Vascular Endothelial Growth Factor Receptor 2, Partially Suppresses and Regresses Laser-Induced Choroidal Neovascularization in a Rat Model

Kim, Jae Hui; Kim, Tae Eun; Kim, Ju-A; Yun, Ji-Hyun; Sohn, Sunyoung; Shim, Sang Ryeol; Lee, Sang Hoon; Kim, Sang Jin

doi:10.1089/jop.2014.0021

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The images of laser spots were observed with a wide pinhole allowing a large depth of field. The area of CNV was measured at a depth where the largest dimension of CNV was observed among the images using Image J program (National Institute of Health, Bethesda, MD, USA) by an ophthalmologist who was not aware of the treatment of the rats as previously described 32 46 .…”

Section: Methodsmentioning

confidence: 99%

Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment

Kim

Lee

Yun

et al. 2015

Sci Rep

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Choroidal neovascularization (CNV) is the hallmark of wet age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. Although the pathogenesis of CNV is not clear, a number of studies show that ocular-infiltrating macrophages and inflammation play a critical role in the development of CNV. TNFα-stimulated gene/protein (TSG)-6 is a multifunctional endogenous protein that has anti-inflammatory activities partly by regulating macrophage activation. Therefore, we here investigated the therapeutic potential of TSG-6 in a rat model of CNV induced by laser photocoagulation. Time course analysis showed that the expression of VEGF and pro-inflammatory cytokines in the choroid was up-regulated early after laser injury, and gradually decreased to baseline over 14 days. An intravitreal injection of TSG-6 suppressed the expression of VEGF and pro-inflammatory cytokines including CCL2, and reduced the size of CNV. Also, the number of Iba+ and CCR2+ cells including infiltrating macrophages was markedly lower in the CNV lesion of TSG-6-treated eyes. Further analysis identified CCR2+ CD11b+ CD11c+ cells and CCR2+ CD11b-CD11c+ cells as the cell populations that were increased by laser injury and reduced by TSG-6 treatment. Together, the results demonstrate that TSG-6 inhibits inflammation and CCR2+ monocyte recruitment into the choroid, and suppresses the development of CNV.

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Section: Methodsmentioning

confidence: 99%

Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment

Kim

Lee

Yun

et al. 2015

Sci Rep

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“…gov identifier NCT01940900). Another anti-VEGFR2 antibody, tanibirumab, has been shown to suppress and regress laser-induced choroidal neovascularization in a rat model (Kim et al ., 2014). This evidence suggests that targeted inhibition of VEGFR2 is a useful strategy for treating neovascular AMD and angiogenesis-related disorders.…”

Section: Discussionmentioning

confidence: 99%

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

Park

Baek

Kim

et al. 2019

Biomolecules & Therapeutics

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Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

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Antibody therapies and their challenges in the treatment of age-related macular degeneration

Volz

Pauly

2015

European Journal of Pharmaceutics and Biopharmaceutics

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Intravitreal Tanibirumab, a Fully Human Monoclonal Antibody Against Vascular Endothelial Growth Factor Receptor 2, Partially Suppresses and Regresses Laser-Induced Choroidal Neovascularization in a Rat Model

Abstract: Intravitreally administered tanibirumab partially suppressed the formation of new CNV and partially regressed preformed laser-induced CNV in the rat model. Tanibirumab may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.

Cited by 4 publications

References 30 publications

Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment

Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

Antibody therapies and their challenges in the treatment of age-related macular degeneration

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