Topical axitinib is a potent inhibitor of corneal neovascularization

Lledó-Riquelme, M.; Campos-Mollo, E.; Fernández‐Sánchez, Laura

doi:10.1111/ceo.13333

Cited by 15 publications

(13 citation statements)

References 42 publications

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“…Topical application of axitinib showed a dose-dependent inhibition of CoNV area and corneal stroma vascularization in a rabbit suture-induced CoNV model. Sunitinib tested using the same methodology showed similar reduction in CoNV with no significant difference in level of CoNV compared to axitinib [43].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 83%

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

2020

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Under healthy conditions, the cornea is an avascular structure which allows for transparency and optimal visual acuity. Its avascular nature is maintained by a balance of proangiogenic and antiangiogenic factors. An imbalance of these factors can result in abnormal blood vessel proliferation into the cornea. This corneal neovascularization (CoNV) can stem from a variety of insults including hypoxia and ocular surface inflammation caused by trauma, infection, chemical burns, and immunological diseases. CoNV threatens corneal transparency, resulting in permanent vision loss. Mainstay treatments of CoNV have partial efficacy and associated side effects, revealing the need for novel treatments. Numerous natural products and synthetic small molecules have shown potential in preclinical studies in vivo as antiangiogenic therapies for CoNV. Such small molecules include synthetic inhibitors of the vascular endothelial growth factor (VEGF) receptor and other tyrosine kinases, plus repurposed antimicrobials, as well as natural source-derived flavonoid and non-flavonoid phytochemicals, immunosuppressants, vitamins, and histone deacetylase inhibitors. They induce antiangiogenic and anti-inflammatory effects through inhibition of VEGF, NF-κB, and other growth factor receptor pathways. Here, we review the potential of small molecules, both synthetics and natural products, targeting these and other molecular mechanisms, as antiangiogenic agents in the treatment of CoNV.

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Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 83%

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

2020

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“…The insignificant effect of axitinib on corneal VEGFR3 may be the result of this attribution. Riquelme et al also demonstrated topical administration of different axitinib concentrations inhibited CNV by preventing both VEGF and platelet-derived growth factor pathways 26 . It was indicated that not only the topical administration, oral use of axitinib also prevented laser-induced choroidal neovascularization 27 .…”

Section: Discussionmentioning

confidence: 97%

Effect of axitinib on inflammation in experimental corneal neovascularization model in rats

Canacankatan¹,

Dinç²,

Kibar³

et al. 2018

Cukurova Medical Journal

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Öz Purpose:This study investigated the antiinflammatory efficacy of topical application of a selective tyrosine kinase receptor inhibitor (TKI), Axitinib in experimental corneal neovascularization (CNV) model in rats. Vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2 and VEGFR3 were evaluated as angiogenic markers, nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNFα) and cyclooxygenase-2 (COX2) were determined as inflammatory markers and also histopathological evaluations were carried out. Materials and Methods: Experimental CNV model was established by silver nitrate cauterization in right eye. 6 groups were included as Control; CNV; CNV+DMSO; CNV+0.04% Axitinib; CNV+0.08% Axitinib and CNV+0.24% Axitinib. The corneas were collected and VEGFR1, VEGFR2, VEGFR3, NF-κB, TNFα and COX2 were measured by ELISA. Results: Axitinib, significantly reduced corneal VEGFR1 and VEGFR2 compared to CNV. The most efficiency of Axitinib treatment was confirmed on VEGFR2 and especially with 0.04% dose. Increased NF-κB and TNFα level were reduced by 0.04% Axitinib treatment compared to CNV and CNV+DMSO. Conclusion: Axitinib may be suggested as a promising anti-inflammatory agent in CNV by suppressing corneal VEGFR1, VEGFR2, NF-κB and TNFα, beside improving the histological pattern.Amaç: Bu çalışmada sıçanlarda deneysel kornea neovaskülarizasyonu (CNV) modelinde bir selektif tirosin kinaz reseptör inhibitörü (TKI), Axitinib' in topikal uygulamasının anti-inflamatuar etkinliği araştırıldı. Vasküler endotelyal büyüme faktörü reseptörü 1 (VEGFR1), VEGFR2 ve VEGFR3 anjiyojenik belirteçler olarak değerlendirildi, nükleer faktör kappa B (NF-κB), tümör nekroz faktörü (TNFα) ve siklooksijenaz-2 (COX2) ise inflamatuar belirteçler olarak belirlendi ve ayrıca histopatolojik değerlendirmeler yapıldı. Gereç ve Yöntem: Sıçanların sağ gözlerinde, gümüş nitrat katerizasyonu ile deneysel CNV modeli oluşturuldu. Kontrol; CNV; CNV+DMSO; CNV+% 0.04 Axitinib; CNV+% 0.08 Axitinib ve CNV+% 0.24 Axitinib olmak üzere çalışmaya 6 grup dahil edildi. Kornealar diseke edildi ve VEGFR1, VEGFR2, VEGFR3, NF-κB, TNFα ve COX2 ELISA yöntemi ile ölçüldü. Bulgular: Axitinib, CNV ile karşılaştırıldığında korneal VEGFR1 ve VEGFR2'i anlamlı olarak azaldı. Axitinib tedavisinin en etkin sonuçları VEGFR2 üzerine ve özellikle % 0,04 dozunda saptandı. Artmış NF-κB ve TNFα seviyesi % 0.04 Axitinib tedavisi ile CNV ve CNV+DMSO'ya göre azaldığı saptandı. Sonuç: Axitinib, VEGFR1, VEGFR2, NF-κB ve TNFα'yı baskılayarak ve ayrıca histolojik paterni iyileştirerek kornea CNV de ümit verici bir anti-inflamatuar ajan olarak önerilebilir.

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“…Most studies on TKIs used to treat CNV have focused on multi-target TKIs that target VEGFR-1/3 and PDGF as well as VEGFR-2 [14,24,25,26,27,28]. Sunitinib had about three times more efficacy than bevacizumab in an animal study, but side-effects, including iris pigmentation, were also reported [14].…”

Section: Discussionmentioning

confidence: 99%

“…There has only been one study about the effects of rivoceranib on CNV [23]. Additionally, several studies on the inhibition of tyrosine kinase pathway for CNV have focused on multi-targeted TKIs [14,24,25,26,27,28]. In this study, we compared the efficacy of topical rivoceranib to that of topical bevacizumab in the murine model of CNV.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization

Yoon

Woo

et al. 2019

Medicina

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Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p < 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model.

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Topical axitinib is a potent inhibitor of corneal neovascularization

Abstract: Topical administration of the three axitinib concentrations inhibited CNV in rabbits, blocking both vascular endothelial growth factor and platelet-derived growth factor pathways. Axitinib at 0.5 mg/mL induced profound inhibition of corneal angiogenesis.

Cited by 15 publications

References 42 publications

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

Effect of axitinib on inflammation in experimental corneal neovascularization model in rats

Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization

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