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对患有早产儿视网膜病变的眼睛的玻璃体液中27种细胞因子水平进行同步分析。

Simultaneous analyses of vitreous levels of 27 cytokines in eyes with retinopathy of prematurity.

作者信息

Sato Tatsuhiko, Kusaka Shunji, Shimojo Hiroshi, Fujikado Takashi

机构信息

Department of Applied Visual Science, Osaka University Medical School, Osaka, Japan.

出版信息

Ophthalmology. 2009 Nov;116(11):2165-9. doi: 10.1016/j.ophtha.2009.04.026. Epub 2009 Aug 22.

Abstract

PURPOSE

To determine the vitreous levels of 27 types of cytokines in eyes with retinopathy of prematurity (ROP).

DESIGN

Retrospective case-control study.

PARTICIPANTS

Twenty-seven eyes of 19 infants with stage 4 ROP were studied. Six eyes of 5 patients with congenital cataract who underwent lensectomy were used as controls.

METHODS

The ROP eyes were divided into 2 groups according to vascular activity: 12 eyes with vascularly active ROP and 15 eyes with vascularly inactive ROP. Undiluted vitreous samples were collected, and the vitreous concentrations of 27 types of cytokines were determined by a multiplex bead analysis system: interleukin (IL)-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, fibroblast growth factor (FGF) basic, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-r, interferon-gamma-inducible protein (IP)-10, monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor bb, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor alpha, and vascular endothelial growth factor (VEGF).

MAIN OUTCOME MEASURES

The vitreous levels of the 27 types of cytokines and a comparison of the levels in the 3 groups.

RESULTS

The postmenstrual age at vitrectomy was significantly younger in the vascularly active ROP eyes than in vascularly inactive ROP eyes. The cytokines that had significantly different vitreous levels among the 3 groups were: IL-6, IL-7, IL-10, IL-15, Eotaxin, FGF basic, G-CSF, GM-CSF, IP-10, RANTES, and VEGF (P<0.05). The vitreous levels of IL-6, IL-7, IL-15, Eotaxin, G-CSF, IP-10, and RANTES were significantly higher (P<0.05) in both vascularly active and inactive ROP eyes than in control eyes, whereas the vitreous level of VEGF was significantly higher (P<0.05) only in vascularly active ROP eyes than in control eyes. There was a significantly negative correlation (r = -0.382; P = 0.0495) between the VEGF level and the postmenstrual age at vitrectomy.

CONCLUSIONS

These results indicate that, although cytokines other than VEGF may be involved in the pathologic changes in eyes with ROP, VEGF is likely to have the strongest correlation with the vascular activity in ROP eyes among these cytokines.

摘要

目的

测定早产儿视网膜病变(ROP)患儿眼内27种细胞因子的玻璃体水平。

设计

回顾性病例对照研究。

研究对象

19例4期ROP婴儿的27只眼。选取5例先天性白内障患者行晶状体切除术后的6只眼作为对照。

方法

根据血管活性将ROP眼分为2组:12只血管活性ROP眼和15只血管非活性ROP眼。采集未稀释的玻璃体样本,采用多重微珠分析系统测定27种细胞因子的玻璃体浓度:白细胞介素(IL)-1β、IL-1受体拮抗剂、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-9、IL-10、IL-12、IL-13、IL-15、IL-17、嗜酸性粒细胞趋化因子、碱性成纤维细胞生长因子(FGF)、粒细胞集落刺激因子(G-CSF)、粒细胞巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ、干扰素-γ诱导蛋白(IP)-10、单核细胞趋化蛋白1、巨噬细胞炎性蛋白(MIP)-1α、MIP-1β、血小板衍生生长因子bb、活化调节正常T细胞表达和分泌因子(RANTES)、肿瘤坏死因子α和血管内皮生长因子(VEGF)。

主要观察指标

27种细胞因子的玻璃体水平及3组间水平比较。

结果

血管活性ROP眼玻璃体切除时的孕龄显著低于血管非活性ROP眼。3组间玻璃体水平有显著差异的细胞因子为:IL-6、IL-7、IL-10、IL-15、嗜酸性粒细胞趋化因子、碱性FGF、G-CSF、GM-CSF、IP-10、RANTES和VEGF(P<0.05)。血管活性和非活性ROP眼的IL-6、IL-7、IL-15、嗜酸性粒细胞趋化因子、G-CSF、IP-10和RANTES玻璃体水平均显著高于对照眼(P<0.05),而VEGF玻璃体水平仅在血管活性ROP眼中显著高于对照眼(P<0.05)。VEGF水平与玻璃体切除时的孕龄呈显著负相关(r = -0.382;P = 0.0495)。

结论

这些结果表明,尽管VEGF以外的细胞因子可能参与ROP患儿眼内的病理变化,但在这些细胞因子中,VEGF可能与ROP眼的血管活性相关性最强。

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