Suppression of Choroidal Neovascularization and Quantitative and Qualitative Inhibition of VEGF and CCL2 by Heparin

Tomida, Daisuke; Nishiguchi, Koji M.; Kataoka, Keiko; Yasuma, Tetsuhiro; Iwata, Eiji; Uetani, Ruka; Kachi, Shu; Terasaki, Hiroko

doi:10.1167/iovs.10-6737

Cited by 18 publications

(13 citation statements)

References 34 publications

(57 reference statements)

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“…First, our subjects included 21 patients who were taking oral medications (19, 6 and 7 were using antihypertensive agents, anticoagulants, and lipid-lowering agents, respectively, with some patients taking multiple drugs) that have been reported to reduce the levels of inflammatory factors such as VEGF [20,21,22]. However, we found no significant differences in the vitreous levels of inflammatory factors (VEGF, sICAM-1 and PEDF) between the 19 patients on antihypertensive therapy and the 21 patients not on antihypertensive therapy, between the 6 patients taking anticoagulants and the 34 patients not taking anticoagulants, and between the 7 patients using lipid-lowering agents and the 33 patients not using such agents.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

et al. 2012

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Concentrations of inflammatory factors were measured in 40 patients with macular edema due to major branch retinal vein occlusion (BRVO) or macular BRVO who were treated by pars plana vitrectomy. Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived factor (PEDF) were determined. Visual acuity and central macular thickness were significantly improved at 6 months in both groups. Vitreous fluid levels of VEGF and sICAM-1 were higher in the major BRVO group than the macular BRVO group, while the PEDF level was lower in the major group than the macular group. The mean visual acuity and central macular thickness at 6 months were not significantly different between the macular and major groups. In conclusion, patients with major BRVO had higher vitreous levels of inflammatory factors and lower vitreous levels of anti-inflammatory PEDF. Accordingly, regulating inflammatory factors might be more important in major BRVO than macular BRVO.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

et al. 2012

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“…These results obtained with eye drop delivery of CPP-anti-VEGF accord well with the results of other published studies using the CNV model to demonstrate the efficacy of a range of anti-VEGF drugs that significantly reduce the area of choroidal neovascularization. [47][48][49][50] In summary, these data indicate the utility of a novel noninvasive eye drop delivery mechanism for nAMD drugs. The CPP-drug eye drops have potential to significantly impact the treatment of nAMD by revolutionizing drug-delivery options.…”

Section: Discussionmentioning

confidence: 75%

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides

Cogan

Hill

Lynch

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

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“…Four spots of laser photocoagulations (532 nm, 180 mW, 100 ms, 75 μm; Novus Verdi; Coherent Inc., Santa Clara, CA, USA) were placed in each fundus of the eye on day 0 by one individual blinded to the group assignment, as described previously (Tomida et al ., ). The laser spots were created around the optic nerve using a slit lamp delivery system and a coverslip was used as a contact lens.…”

Section: Methodsmentioning

confidence: 97%

“…Mouse VEGF (mVEGF) levels were measured with an elisa as described previously (Nishiguchi et al ., ; Tomida et al ., ). Briefly, 3 days after laser photocoagulation, protein lysates were prepared from the RPE/choroid complex with the same procedure as above, and the level of VEGF was measured with mVEGF elisa (MMV‐00; R&D Systems) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 97%

Histamine H₄ receptor as a new therapeutic target for choroidal neovascularization in age‐related macular degeneration

Kaneko

Ijima

et al. 2014

British J Pharmacology

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Background and Purpose The present treatment for choroidal neovascularization (CNV) associated with age‐related macular degeneration (AMD) is not sufficient. Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice. Experimental Approach H4 receptor expression was examined in CNVs from patients with AMD. In mice, laser photocoagulation was performed in the retina to induce experimental CNV (laser CNV). Protein and mRNA expression levels were determined and CNV volume measured in wild‐type and Hrh4‐/‐ mice with laser CNV. The effects of JNJ7777120, an H4 receptor antagonist, administered intravitreously, on CNV volume and pathological vessel leakage were determined in mice with laser CNV and controls. Fundus imaging, retinal histology and electroretinography were performed on eyes injected with JNJ7777120 to evaluate retinal toxicity. Key Results Human H4 receptors were only confirmed in CNV samples from AMD patients and not in the other subretinal tissues. Mouse H4 receptors were expressed in retinal pigment epithelium only after inducing laser CNV in wild‐type mice, and were co‐localized with the macrophage marker F4/80. Laser CNV volume was reduced in Hrh4‐/‐ mice compared with that in wild‐type mice, and JNJ7777120 suppressed laser‐induced CNV volume and pathological CNV leakage in wild‐type mice. Also eyes injected with JNJ7777120 did not show retinal degeneration. Conclusions and Implications H4 receptors are expressed in macrophages that accumulate around CNVs. Suppressing H4 receptor expression prevented the pathological vessel leakage without showing retinal toxicity, indicating that the H4 receptor has potential as a novel therapeutic target in AMD.

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Suppression of Choroidal Neovascularization and Quantitative and Qualitative Inhibition of VEGF and CCL2 by Heparin

Abstract: Intravitreal heparin injection inhibited CNV development. Reduced VEGF and CCL2 secretion by RPE cells and suppression of VEGF-VEGFR2 and CCL2-CCR2 interactions at the laser site mediated by heparin may contribute to the pharmacologic effect.

Cited by 18 publications

References 34 publications

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides

Histamine H₄ receptor as a new therapeutic target for choroidal neovascularization in age‐related macular degeneration

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Suppression of Choroidal Neovascularization and Quantitative and Qualitative Inhibition of VEGF and CCL2 by Heparin

Abstract: Intravitreal heparin injection inhibited CNV development. Reduced VEGF and CCL2 secretion by RPE cells and suppression of VEGF-VEGFR2 and CCL2-CCR2 interactions at the laser site mediated by heparin may contribute to the pharmacologic effect.

Cited by 18 publications

References 34 publications

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

Inflammatory Factors in Major and Macular Branch Retinal Vein Occlusion

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides

Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age‐related macular degeneration

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Histamine H₄ receptor as a new therapeutic target for choroidal neovascularization in age‐related macular degeneration