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雷珠单抗治疗对新生血管性年龄相关性黄斑变性患者细胞外基质的影响。

Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration.

作者信息

Nita Małgorzata, Michalska-Małecka Katarzyna, Mazurek Urszula, Kimsa Małgorzata, Strzałka-Mrozik Barbara, Grzybowski Andrzej, Romaniuk Dorota

机构信息

Domestic and Specialized Medicine Centre "Dilmed", Katowice, Poland.

Department of Ophthalmology, Medical University of Silesia, Independent Public Clinical Hospital, Katowice, Poland.

出版信息

Med Sci Monit. 2014 May 28;20:875-83. doi: 10.12659/MSM.890031.

Abstract

BACKGROUND

We know the influence of the intravitreal anti-vascular endothelial growth factor (VEGF) injections on the choroidal neovascularization in the course of exudative age-related macular degeneration (AMD). However, the influence of the ranibizumab therapy in question on the extracellular matrix (ECM) remains unknown. We aimed to estimate the influence of Lucentis intravitreal injections on the gene expression of structural components of the extracellular matrix in patients with neovascular AMD.

MATERIAL AND METHODS

Patients with subfoveal localization of neovascularization in AMD, which was clinically active and observed using optical coherence tomography, were treated with ranibizumab (0.5 mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from peripheral blood mononuclear cells, and an oligonucleotide microarray technique enabled comparison of the expression level of genes encoding collagens, elastin, and laminins in AMD patients compared to control subjects.

RESULTS

After 3 intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed increased expression, whereas decreased expression mainly occurred for the following genes: COL4A5, COL11A1, OL4A6C, LAMB4, and LAMC2.

CONCLUSIONS

Anti-VEGF local therapy influences the gene expression of structural components of the ECM as measured from blood samples. The loading dose of ranibizumab for the retina changes the expression of collagen and laminin genes, but does not influence the expression of the elastin gene.

摘要

背景

我们了解玻璃体内注射抗血管内皮生长因子(VEGF)对渗出性年龄相关性黄斑变性(AMD)病程中脉络膜新生血管形成的影响。然而,上述雷珠单抗治疗对细胞外基质(ECM)的影响仍不清楚。我们旨在评估雷珠单抗玻璃体内注射对新生血管性AMD患者细胞外基质结构成分基因表达的影响。

材料与方法

对AMD患者中黄斑中心凹下新生血管形成且临床活动、采用光学相干断层扫描观察的患者,按照PrONTO方案用雷珠单抗(0.5mg/0.05mL)治疗。从外周血单个核细胞中提取总RNA,寡核苷酸微阵列技术能够比较AMD患者与对照受试者中编码胶原蛋白、弹性蛋白和层粘连蛋白的基因表达水平。

结果

玻璃体内注射3次雷珠单抗(Lucentis)后,COL1A1和COL6A1基因表达增加,而以下基因主要出现表达降低:COL4A5、COL11A1、OL4A6C、LAMB4和LAMC2。

结论

抗VEGF局部治疗影响从血样中检测到的ECM结构成分的基因表达。雷珠单抗用于视网膜的负荷剂量改变胶原蛋白和层粘连蛋白基因的表达,但不影响弹性蛋白基因的表达。

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