Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

Kang, Seungbum; Park, Ki Cheol; Yang, Keum‐Jin; Choi, Hyunsu; Kim, So‐Hee; Roh, Yong Kyun

doi:10.1111/j.1442-9071.2012.02813.x

Cited by 9 publications

(13 citation statements)

References 36 publications

(85 reference statements)

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“…Park et al investigated the effect of sorafenib, an orally administered, multi-targeted receptor tyrosine kinase inhibitor, on CNV progression in a rat CNV model, and showed that the drug inhibited laser-induced CNV [27]. Kang and co-workers evaluated the anti-angiogenic effects of the VEGF receptor tyrosine kinase inhibitor, cediranib, in an experimental laser-induced CNV model [28]. They found that oral administration of cediranib inhibited CNV growth.…”

Section: Discussionmentioning

confidence: 99%

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

et al. 2015

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BackgroundThis two-phase experimental study was conducted to determine the maximum safe dose of intravitreal imatinib (IVI) and its inhibitory effect on a rat model of choroidal neovascularization (CNV).MethodsIn phase I, 60 rats were divided into six groups (A to F); five of which received IVI with concentrations of 330 (A), 250 (B), 165 (C), 80 (D), and 40 (E) µg/5 µl, and the control group (F) received balanced salt solution (BSS). In addition to electroretinography (ERG), routine histopathological analysis and immunohistochemistry for glial fibrillary acidic protein were performed. In phase II, CNV was induced by laser photocoagulation in 25 rats and the animals were divided into two groups. One group received the maximum safe dose of IVI, determined in phase I, and the other received intravitreal BSS. After 4 weeks, the groups were compared in terms of mean scores of fluorescein leakage in fluorescein angiography and the mean CNV areas in histopathological sections.ResultsIn phase I, ERG and the histopathological findings revealed retinal toxicity in groups A to D and A to C, respectively; therefore, a dose of 40 µg/5 µl imatinib was specified as the maximum safe dose for phase II. In phase II, late phase fluorescein leakage and the CNV areas were not significantly different between the imatinib-treated eyes and the controls (p = 0.62 and p = 0.5, respectively).ConclusionsDespite the safety of IVI with a dose of 40 µg/5 µl, no inhibitory effect on laser-induced CNV was observed. Further studies are required to investigate the possible synergistic effects of Imatinib with conventional anti-CNV drugs.

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Section: Discussionmentioning

confidence: 99%

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

et al. 2015

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“…16 Briefly, after general anesthesia was induced via an intraperitoneal injection of 30 mg zolazepam (Zoletil; Virbac, Carros, France) and 10 mg xylazine hydrochloride (Rompun; Bayer, Leuverkeusen, Germany) per kilogram of body weight, laser-induced rupture of Bruch's membrane was performed on both eyes. Five laser spots were created per eye and delivered by slit lamp (SL120; Carl Zeiss Meditec, Jena, Germany).…”

Section: Animal Model Of Cnvmentioning

confidence: 99%

“…Fourteen days after laser injury, mice in each group were anesthetized and perfused through the left ventricle with 1.0 mL PBS containing 25 mg fluorescein isothiocyanatedextran (molecular weight, 2 3 10 6 kDa; Sigma-Aldrich Corp.), as described previously. 16,17 Eyes were enucleated and fixed in 4% paraformaldehyde for 1 hour. Retinal pigment epitheliumchoroid-sclera eyecups were prepared after hemisecting the eye, with total removal of the lens, vitreous body, and retina.…”

Section: Preparation Of Choroidal Flat Mountsmentioning

confidence: 99%

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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“…Thirty mice were randomly divided into three groups: vehicle‐treated mice ( n = 10), ALS‐L1023 (100 mg/kg/day)‐treated mice ( n = 10) and ALS‐L1023 (200 mg/kg/day)‐treated mice ( n = 10). Non‐treated mice (without vehicle) were not evaluated in the present study because our previous studies already demonstrated that vehicle (DMSO/0.5% carboxymethyl cellulose) does not cause any effect on CNV development . Vehicle and ALS‐L1023 treatment commenced at the onset of the experiments (day 0).…”

Section: Methodsmentioning

confidence: 99%

Anti‐angiogenic effect of ALS‐L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice

Roh

Jee

Rho

et al. 2015

Clinical Exper Ophthalmology

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Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

Abstract: Background: This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization.

Cited by 9 publications

References 36 publications

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

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

Anti‐angiogenic effect of ALS‐L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice

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