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结膜下注射托珠单抗对大鼠碱烧伤诱导的角膜新生血管形成的抑制作用。

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

作者信息

Sari Esin Sogutlu, Yazici Alper, Aksit Hasan, Yay Arzu, Sahin Gözde, Yildiz Onur, Ermis Sitki Samet, Seyrek Kamil, Yalcin Betul

机构信息

Department of Ophthalmology, Faculty of Medicine, Balıkesir University , Balıkesir , Turkey .

出版信息

Curr Eye Res. 2015 Jan;40(1):48-55. doi: 10.3109/02713683.2014.914541. Epub 2014 Jun 9.

Abstract

BACKGROUND

To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats.

METHODS

Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA.

RESULTS

The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

摘要

背景

评估结膜下注射白细胞介素-6受体(IL-6R)抗体(托珠单抗)对大鼠碱烧伤诱导的角膜新生血管化(CNV)的影响。

方法

在24只大鼠的24只右眼上造成碱烧伤诱导的角膜新生血管化。然后将大鼠随机分为2组。第1组在碱烧伤第5天接受结膜下注射4mg/0.2ml托珠单抗,第2组接受结膜下注射0.2ml生理盐水。根据照片计算角膜新生血管侵入的表面积。在第15天处死大鼠并切除角膜。角膜标本用苏木精-伊红染色以评估组织形态,并用血管性血友病因子(vWF)进行免疫组织化学染色以评估微血管结构。通过酶联免疫吸附测定(ELISA)分析血管内皮生长因子(VEGF)表达。

结果

第1组CNV的面积百分比为26.9%,第2组为56.5%(p<0.001)。组织学评估显示,结膜下注射托珠单抗未明显改变角膜结构。第1组的角膜炎症评分明显低于第2组(p<0.001)。第2组中vWF染色的血管数量明显高于第1组(分别为15.23和5.46;p<0.001)。ELISA分析显示,与第2组相比,第1组角膜VEGF水平明显降低(p=0.013)。结论:本数据首次证明结膜下注射托珠单抗对减少大鼠角膜碱烧伤模型中的CNV有有益作用。有必要进行进一步研究以证实这些发现用于临床应用。

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