Bevacizumab Application Delays Epithelial Healing in Rabbit Cornea

Kim, Tae Im; Chung, J. N.; Hong, Jin Pyo; Min, Kyung; Seo, Kyoung Yul; Kim, Eung Kweon

doi:10.1167/iovs.08-2805

Cited by 84 publications

(74 citation statements)

References 32 publications

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“…Although anti-VEGF therapy is effective for blocking corneal neovascularization, delayed corneal wound healing is a significant problem (Dastjerdi et al 2009;Kim et al 2009). Although blocking of lymphangiogenesis alone may inhibit the induction of an immune response, blood vessels could still grow to supply the graft with nutrients and promote wound healing.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

Hayashi

Usui

Yamagami

2016

Tohoku J. Exp. Med.

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When a transparent cornea becomes opaque due to infectious diseases, trauma, or ophthalmic surgery, the impaired cornea is replaced with a donor cornea to improve visual function. In this corneal transplantation, the graft survival rate is comparatively high, partly because of lacking vascular and lymphatic vessel in cornea. However, the transplanted corneas sometimes become opaque if allograft rejection occurs. Suppression of allograft rejection is critical for favorable outcomes of corneal transplantation. The essential effects of endogenous monomeric soluble vascular endothelial growth factor receptors (VEGFRs) 1 and 2 have been reported in corneal angiogenesis and lymphangiogenesis. This study investigated the effects of dimeric soluble VEGFR2/Fc chimera protein on corneal allograft rejection for future clinical application. Allogeneic full-thickness corneal transplantation was performed in C57BL/6 to BALB/c mice. The recipients were treated by intrastromal injection of soluble VEGFR1/Fc chimera (sR1/Fc group), soluble VEGFR2/Fc chimera (sR2/Fc group), or human IgG1/Fc protein (IgG/Fc group) at 0, 7, and 14 days after surgery. Both hemangiogenesis and lymphangiogenesis were significantly suppressed in the corneas of the sR2/Fc group compared with the IgG/Fc group. All grafts failed due to corneal wound rupture in the sR1/Fc group. In the sR2/Fc group, respective donor-derived MHC class II + /CD11c + cells and CD11b-positive macrophage infiltration were reduced in the DLNs and the corneas showing a negative delayed-type hypersensitivity, compared with the IgG/Fc group. Our findings demonstrate that soluble VEGFR2/Fc chimera protein efficiently suppresses corneal allo-rejection, while reducing hemangiogenesis and lymhangiogenesis, and immune-competent cell-trafficking and may be a powerful tool for corneal allograft survival.

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Section: Discussionmentioning

confidence: 99%

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

Hayashi

Usui

Yamagami

2016

Tohoku J. Exp. Med.

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“…A comparação entre os dois grupos não mostrou um atraso na re-epitelização do grupo estudo, sugerindo segurança da droga em situações de defeito epitelial. Trabalhos recentes mostram um atraso no fechamento epitelial (27) contrastando com o resultado encontrado no presente estudo. Entretanto, o tratamento foi realizado com bevacizumabe tópico várias vezes ao dia, no qual a droga tem um contato direto com o epitélio corneano; enquanto no presente trabalho foi realizado aplicação subconjuntival, em que a droga não atinge as células epiteliais diretamente.…”

Section: Discussionunclassified

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

Mello¹,

Lupion²,

Oliveira³

et al. 2011

Arq. Bras. Oftalmol.

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Nota Editorial: Depois de concluída a análise do artigo sob sigilo editorial e com a anuência do Dr. Vinícius Coral Ghanem e Procópio Miguel dos Santos sobre a divulgação de seu nome como revisor, agradecemos sua participação neste processo.Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química ABSTRACT Purposes:To evaluate the effect of subconjunctival bevacizumab in an experimental model of neovascularization in rabbit cornea. Determine its effect on vessels extension, inflammation, epithelialization of the cornea and whether the evaluation method used is appropriate to compare neovascular models. Methods: Experimental, prospective, randomized, blinded study in twenty rabbits subjected to chemical trauma with sodium hydroxide at 1N divided into two groups. The study group received subconjunctival injection of 0.15 ml (3.75 mg) of bevacizumab and was compared with the control group that received subconjunctival injection of 0.15 ml saline solution. After 25 days, digital photographic analysis was performed to assess the vessel's extension and inflammation/diameter according to pre-established criteria. Histopathology of the cornea, which evaluated the state of the epithelium and the number of polymorphonuclear cells was also studied. Results:The length of the neovessels was greater in the control group compared to the study group (P=<0.001). There was no difference in inflammation/vessel diameter between groups. Histopathology analysis showed that there was no difference between groups for the variables state of the epithelium and number of polymorphonuclear cells. The concordance analysis for the variable extension of the vessels and the variable inflammation/vessel diameter was estimated with Kappa coefficients of 0.705 and 0.500 respectively, indicating a good level of agreement in different evaluations and validating the method. Conclusions:The experimental model is adequate and can be reproduced to evaluate other drugs in the cornea. Bevacizumab inhibit the neovessels' growth but was not effective in preventing the inflammatory response. The drug did not delay the reepithelialization of the cornea.

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“…Macrophages are known to trigger neovascularization in ischemic or inlamed corneas [63]. There is a concern about the interference of the topical form but not subconjunctival form of bevacizumab with nerve regeneration and delayed wound healing [54,64,65].…”

Section: Anti-vegf Antibodymentioning

confidence: 99%

Corneal Angiogenesis: Etiologies, Complications, and Management

Feizi¹

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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A large subset of corneal pathologies involves the formation of new blood vessels, leading to compromised visual acuity. Additionally, neovascularization of the cornea worsens the prognosis of subsequent penetrating keratoplasty, keeping the patient in a vicious circle of poor prognosis. Ocular angiogenesis results from the upregulation of proangiogenic and downregulation of antiangiogenic factors. There is a tremendous need for developing efective measures to prevent and/or treat corneal neovascularization. Topical steroid medication, cautery, argon and yellow dye laser, and ine needle diathermy have all been advocated with varying degrees of success. The process of corneal neovascularization is primarily mediated by the vascular endothelial growth factor family of proteins, and current therapies are aimed at disrupting the various steps in this pathway. This article aims to review the clinical causes and presentations of corneal neovascularization caused by diferent etiologies. Moreover, this chapter reviews diferent complications caused by corneal neovascularization and summarizes the most relevant treatments available so far.

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Bevacizumab Application Delays Epithelial Healing in Rabbit Cornea

Abstract: Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.

Cited by 84 publications

References 32 publications

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

Corneal Angiogenesis: Etiologies, Complications, and Management

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