Inhibitory effects of bevacizumab on angiogenesis and corneal neovascularization

Han, Youngnam; Lee, Ji Eun; Jung, Ji Won; Lee, Jong Soo

doi:10.1007/s00417-008-0976-3

Cited by 38 publications

(24 citation statements)

References 18 publications

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“…In vivo observation on days 7 and 21, however, revealed more vessels with visible flow than were visible in high magnification photographs. Consequently, in vivo imaging may be a more sensitive method to assess active vessel presence in the cornea after therapy than current methods using photography [16,17,22,28,30] or flourescein angiography [10,26,29,31]. At day 21, some persistent vessels were found in the cornea in all groups, and likely reflected their maturity as confirmed by perivascular NG2 staining in this study, and earlier findings of αSMA+NG2+ cells lining vessels 7 days after stimulus in our model [33].…”

Section: In Vivo Imaging Of Human Corneal Capillary Regression: Reporsupporting

confidence: 75%

“…In both clinical and experimental studies, corneal capillary regression is commonly evaluated by degree of vascular invasion at the tissue level, using photography of visible blood vessels, fluorescein angiography, or by immunostaining of vascular endothelium at fixed time points [17,[21][22][23][24][25][26][27][28][29][30][31][32]. Little, however, is known about the morphologic characteristics of regressing capillaries at the cellular level following therapy.…”

Section: Introductionmentioning

confidence: 99%

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Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

2011

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Abstract:In this study, we introduce a technique for repeated, microscopic observation of single regressing capillaries in vivo in inflamed murine corneas. Natural capillary regression was initiated by removal of inflammatory stimulus during an active pro-angiogenic phase, while the additional impact of anti-angiogenic treatment with triamcinolone or bevazicumab was investigated. Capillaries regressed naturally within one week and treatments did not further enhance the natural regression. Morphologically, early-phase regression was characterized by significant lumen narrowing and a significant reduction in CD11b+ myeloid cell infiltration of the extracellular matrix. By one week, vascular remodeling occurred concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary walls. Empty conduits without blood flow, positive for collagen IV and devoid of vascular endothelium and pericytes, were apparent in vivo and by three weeks were more numerous than perfused capillaries. By three weeks, macrophages aggregated around remaining perfused capillaries and were observed in apposition with degrading capillary segments. Abrupt termination of capillary sprouting in our regression model further revealed vascular endothelial abandonment of sprout tips and perfused capillary loop formation within a single angiogenic sprout, possibly as an intussusceptive response to cessation of the stimulus. Finally, we observed lumen constriction and macrophage localization on capillary walls in vivo in a clinical case of corneal capillary regression that paralleled findings in our murine model.

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Section: In Vivo Imaging Of Human Corneal Capillary Regression: Reporsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

2011

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“…34,35 In addition, bevacizumab was demonstrated to reduce VEGF-induced permeability and proliferation of cultured porcine choroidal endothelial cells, 18 inhibit VEGF-stimulated proliferation of monkey choroidal endothelial cells, 33 and inhibit VEGF-induced migration of HUVEC. 36 In contrast to these studies, bevacizumab was shown to have a stimulatory effect on cell proliferation in the rat retinal ganglion cell line RGC-5, which was suggested to be due to a nonspecific effect via increasing the protein contents of the cell growth environment. 37 Since 2009, there have been increasing number of studies that have compared the properties of ranibizumab and bevacizumab and investigated their impact on physiological retinal cell functioning.…”

mentioning

confidence: 73%

Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab

Meyer

Holz

2011

Eye

115

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Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a fulllength antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the shortterm toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other.

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“…Han et al [29] investigated the inhibitory effect of subconjunctival bevacizumab on CNV by means of subconjunctival injection of 25 mg/ml bevacizumab after corneal chemical burn injury. On days 3 and 8 after the subconjunctival injection, bevacizumab-treated eyes showed Color version available online less neovascular growth than eyes treated with balanced salt solution.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Its Topical Form in Experimental Rats

et al. 2011

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Background: To compare the effect of different dosages of subconjunctival bevacizumab with its topical administration on preventing the development of corneal neovascularization (CNV) in a rat model of corneal chemical injury. Methods: Neovascularization was induced by pressing a 2-mm diameter alkaline-coated applicator on the central cornea of the right eye of 50 anesthetized male rats. Immediately after cauterization, rats were divided randomly into 5 groups. Groups 1–4 received a subconjunctival injection of 0.02 ml of normal saline (control) or 1, 5 and 25 mg/ml of bevacizumab, respectively. In the fifth group, topical bevacizumab was instilled daily for 7 consecutive days. After 7 days, digital photographs of the cornea were taken and the area of the neovascularized cornea was calculated. Results: Analysis of digital photographs showed that, compared with the controls, a single subconjunctival injection of at least 0.1 mg of bevacizumab (5 mg/ml) – immediately after corneal cauterization – effectively decreased CNV after 7 days. Injection of 25 mg/ml of bevacizumab in the fourth group increased the avascular area more than twofold, compared with the saline-treated group (32.2% compared with 15%, p < 0.001). This difference between groups 4 and 2 was statistically significant (p = 0.04). Although topical delivery of 25 mg/ml bevacizumab was effective to inhibit CNV (p = 0.004), the results were similar to those of the third group. Qualitative microscopic evaluation of the cornea was compatible with the gross findings, as bevacizumab-treated groups had less intense corneal vessel channels and inflammation. Conclusion: Both subconjunctival and topical bevacizumab can prevent CNV in rats.

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Inhibitory effects of bevacizumab on angiogenesis and corneal neovascularization

Abstract: Bevacizumab effectively inhibits angiogenesis and corneal neovascularization, and could be used as a inhibitor of corneal neovascularization in the future.

Cited by 38 publications

References 18 publications

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model

Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab

Prevention of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Its Topical Form in Experimental Rats

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