Safety Profile of Topical VEGF Neutralization at the Cornea
Safety Profile of Topical VEGF Neutralization at the Cornea
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DOI：
10.1167/iovs.07-1129
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Cursiefen, Claus
中科院分区：
文献类型：
--
作者：
Bock, Felix;Onderka, Jasmine;Cursiefen, Claus
目的.贝伐单抗滴眼液抑制角膜新生血管形成。本研究的目的是分析VEGF-A在眼表中和的安全性。将贝伐单抗滴眼液（5 mg/mL）和抗尿VEGF-A抗体（250 μ g/mL）应用于正常小鼠角膜，每天5次，持续7天和14天。随后，通过光学显微镜和电子显微镜分析角膜的形态学变化。在角膜上皮擦伤的小鼠模型中，分析了局部应用的抗VEGF抗体对上皮伤口愈合的影响：治疗组接受贝伐单抗（5 mg/mL）或抗尿VEGF-A抗体（250 μ g/mL）作为滴眼剂，对照组接受等体积的盐水溶液。在12、18和24小时后，在有和没有荧光素染色的情况下对角膜进行体内拍照以进行形态测定。然后处死小鼠，取眼进行组织学、Ki 67/DAPI免疫组织化学和电子显微镜检查。中期抗VEGF治疗对角膜神经密度的影响通过用FITC缀合的抗神经丝抗体处理的角膜染色和形态测定分析来评估。用两种不同类型的抗VEGF抗体滴眼液处理的小鼠角膜在光镜和电镜水平上未显示出明显的角膜形态学变化。此外，抗VEGF抗体滴眼液对角膜上皮损伤后的伤口愈合过程或正常小鼠角膜神经纤维密度没有显著影响。在角膜表面局部中和VEGF-A对正常角膜上皮伤口愈合、正常角膜完整性或正常神经纤维密度没有显著的副作用。因此，抗VEGF滴眼液似乎是治疗角膜新生血管的相对安全的选择。（Invest Ophthalmol维斯科学。2009;50：2095-2102）DOI：10.1167/iovs.07-1129
PURPOSE. Bevacizumab eyedrops inhibit corneal neovascularization. The purpose of this study was to analyze the safety profile of VEGF-A neutralization at the ocular surface.METHODS. Bevacizumab eyedrops (5 mg/mL) and an antimurine VEGF-A antibody (250 mu g/mL) were applied to normal murine corneas five times a day for 7 and 14 days. Subsequently, corneas were analyzed for morphologic changes by light and electron microscopy. In a mouse model of corneal epithelial abrasion, the effects of topically applied anti-VEGF antibodies on epithelial wound healing were analyzed: the treatment group received bevacizumab (5 mg/mL) or the antimurine VEGF-A antibody (250 mu g/mL) as eyedrops, and the control group received an equal volume of saline solution. After 12, 18, and 24 hours, corneas were photographed in vivo with and without fluorescein staining for morphometry. Afterwards the mice were killed, and eyes were removed for histology, immunohistochemistry with Ki67/DAPI, and electron microscopy. The effect of midterm anti-VEGF therapy on corneal nerve density was assessed by staining corneas treated with an FITC-conjugated anti-neurofilament antibody and morphometric analysis.RESULTS. Murine corneas treated with two different types of anti-VEGF antibody eyedrops did not show obvious corneal morphologic changes at the light and electron microscopic levels. Furthermore, anti-VEGF antibody eyedrops had no significant impact on the wound healing process after corneal epithelial injury or on normal murine corneal nerve fiber density.CONCLUSIONS. Topical neutralization of VEGF-A at the corneal surface does not have significant side effects on normal corneal epithelial wound healing, normal corneal integrity, or normal nerve fiber density. Therefore, anti-VEGF eyedrops seem to be a relatively safe option to treat corneal neovascularization. (Invest Ophthalmol Vis Sci. 2009;50:2095-2102) DOI:10.1167/iovs.07-1129