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贝伐珠单抗改变糖尿病性纤维血管膜中的血管微环境。

Altered vascular microenvironment by bevacizumab in diabetic fibrovascular membrane.

机构信息

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Retina. 2013 May;33(5):957-63. doi: 10.1097/IAE.0b013e3182753b41.

DOI:10.1097/IAE.0b013e3182753b41
PMID:23503340
Abstract

PURPOSE

The purpose of this study was to evaluate the impact of intravitreal bevacizumab (IVB) on three cellular components (vascular endothelial cells, pericytes, and myofibroblasts) of the vascular microenvironment in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy.

METHODS

Immunohistological studies with antibodies of CD34, αSMA, and transforming growth factor-β were performed on 20 surgical specimens obtained during a pars plana vitrectomy from 8 IVB-treated eyes, whereas 12 remained untreated. Four different indexes of vascular phenotype (vascular area, vascular major axis, CD34 endothelial area, and blood vessel density) and αSMA expression in vascular and stromal components were quantitatively analyzed.

RESULTS

The intraluminal area of blood vessels, CD34 endothelial area, and the blood vessel density in IVB-treated FVMs were significantly less than in untreated FVMs. The number of CD34 blood vessels in IVB-treated FVMs was similar to that in untreated FVMs. Intravitreal bevacizumab could not affect vascular and stromal αSMA area significantly. However, the ratio of vascular αSMA area/CD34 area was significantly higher in IVB-treated FVMs than in untreated FVMs. Transforming growth factor-β expression could be observed in the IVB-treated FVM.

CONCLUSION

Intravitreal bevacizumab might primarily affect blood vessels, and the effects on pericytes and myofibroblasts might be secondary. Intravitreal bevacizumab treatment regulates vascular microenvironment by the contraction of blood vessels, the increasing pericyte ratio, and transforming growth factor-β expression in FVMs of patients with proliferative diabetic retinopathy.

摘要

目的

本研究旨在评估玻璃体内注射贝伐单抗(IVB)对增生性糖尿病视网膜病变患者纤维血管膜(FVM)血管微环境中三种细胞成分(血管内皮细胞、周细胞和肌成纤维细胞)的影响。

方法

对 8 例接受 IVB 治疗的眼行玻璃体切除术时获得的 20 例手术标本进行 CD34、αSMA 和转化生长因子-β 抗体的免疫组织化学研究,而 12 例未接受治疗。定量分析了 4 种不同的血管表型指标(血管面积、血管长轴、CD34 内皮面积和血管密度)和血管及基质成分中 αSMA 的表达。

结果

IVB 治疗的 FVM 中管腔面积、CD34 内皮面积和血管密度明显小于未治疗的 FVM。IVB 治疗的 FVM 中 CD34 血管数量与未治疗的 FVM 相似。玻璃体内注射贝伐单抗不能显著影响血管和基质的αSMA 面积。然而,IVB 治疗的 FVM 中血管 αSMA 面积/CD34 面积的比值明显高于未治疗的 FVM。在 IVB 治疗的 FVM 中可以观察到转化生长因子-β的表达。

结论

玻璃体内注射贝伐单抗可能主要影响血管,对周细胞和肌成纤维细胞的影响可能是次要的。玻璃体内注射贝伐单抗通过收缩血管、增加周细胞比例和在增生性糖尿病视网膜病变患者的 FVM 中表达转化生长因子-β来调节血管微环境。

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