Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott; Bainbridge, James; Gale, David C.; Pierre, Esaie; Krauss, Achim H.-P.; Adamson, Peter; Shima, David T.; Ng, Y. Jack

doi:10.1016/j.ajpath.2015.04.029

Cited by 28 publications

(44 citation statements)

References 32 publications

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“…Conversely, JR5558 mice may harbor a mutation of Rd8, a retinal degeneration gene (132); therefore, interpretation of retinal neuronal pathologies in aged JR5558 mice requires some caution. Nevertheless, this new model provides a useful tool for the study of RAP and AMD, as well as for evaluating potential therapeutics for both diseases, such as IL-18 immunotherapy and C-C chemokine receptor type 3 antagonists (130)(131)(132)(133)(134)(135).…”

Section: Jr5558 Micementioning

confidence: 99%

Animal models of ocular angiogenesis: from development to pathologies

et al. 2017

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Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.

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Section: Jr5558 Micementioning

confidence: 99%

Animal models of ocular angiogenesis: from development to pathologies

et al. 2017

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“…Choroidal neovascularisation (CNV), a common vision-threatening complication (16), accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration (17)(18)(19). Its pathogenesis involves a disruption of the homeostasis between the retinal pigment epithelium and Bruch's membrane (20).…”

Section: Choroidal Neovascularizationmentioning

confidence: 99%

99Tc-MDP treatment for the therapy of rheumatoid arthritis, choroidal neovascularisation and Graves' ophthalmopathy

Yang

et al. 2016

Biomedical Reports

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Abstract. Technetium 99 conjugated with methylene diphosphonate, which is an anti-inflammatory drug, can inhibit macrophage infiltration and downregulate a number of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Recently, numerous studies have indicated that it could improve rheumatoid arthritis (RA) activity by upregulating the frequency of peripheral γδ T cells and cluster of differentiation CD4 + CD25 + Foxp3 + Tregs, affecting the serum cytokine environment, inhibiting osteoclast formation and reducing the concentrations of rheumatoid factor-immunoglobulin M (IgM)/IgG/IgA. As well, it may have a therapeutic role for choroidal neovascularisation (CNV) and Graves' ophthalmopathy (GO). Therefore, it will be a valuable choice in the treatment of RA, CNV and GO.

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“…Although the CCR3-eotaxin pathway has been shown to be involved in ocular pathological angiogenesis in choroidal neovascularization (CNV) [11][12][13][22][23][24] and in corneal angiogenesis [9,10] , to our knowledge, this is the first report to dem- onstrate a role for CCR3-eotaxin pathways in retinal neovascularization. Historically, the CCR3-eotaxin pathway has been known to contribute to eosinophil migration in allergic reactions [25] .…”

Section: Discussionmentioning

confidence: 99%

“…In the experimental mouse model of CNV, systemic anti-CCR3 treatment reduced CNV [12,13] . CCR3 was previously shown to be a target in allergic disease, and various oral CCR3 antagonists have been developed [30][31][32][33] .…”

Section: Discussionmentioning

confidence: 99%

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Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice

et al. 2017

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Purpose: To investigate the association between retinal neovascularization and the CC chemokine receptor-3 (CCR3) in a mouse model of oxygen-induced retinopathy (OIR). Methods: An OIR model in C57BL/6J mice was used as a retinal neovascularization model. An enzyme-linked immunosorbent assay was performed to evaluate the chronological change in vascular endothelial growth factor A (VEGF-A) and eotaxin expressions. CCR3 and VEGF subtype expression in the retina was examined using real-time RT-PCR, and CCR3, eotaxin, VEGF-A, and CD31 expression was examined immunohistochemically. A CCR3 neutralizing antibody (Ab) was injected into the vitreous humor on both postnatal days 12 (P12) and 14 (P14). Retinal neovascularizations were quantified by measurement of the percentages of neovascular area. Results: The mean eotaxin and VEGF-A protein level was significantly downregulated at P10 and P12 and was significantly upregulated at P14 and P17 (p < 0.05). CCR3 mRNA expression was significantly upregulated at P12 (p < 0.05). VEGF164 mRNA expression was significantly upregulated at P14 (p < 0.05). The areas of vaso-obliteration and neovascularization were significantly suppressed in anti-CCR3 Ab-treated eyes (p < 0.05). Anti-CCR3 Ab treatment suppressed VEGF and eotaxin but not monocyte chemoattractant protein-1. And VEGF 164 mRNA but not VEGF120 mRNA was suppressed by anti-CCR3 Ab treatment. Conclusions: The present data suggest that anti-CCR3 treatment can suppress retinal neovascularization. Anti-CCR3 treatment may have potential as a new therapy for retinopathies with retinal neovascularization such as diabetic retinopathy and retinopathy of prematurity.

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Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

Cited by 28 publications

References 32 publications

Animal models of ocular angiogenesis: from development to pathologies

Animal models of ocular angiogenesis: from development to pathologies

99Tc-MDP treatment for the therapy of rheumatoid arthritis, choroidal neovascularisation and Graves' ophthalmopathy

Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice

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