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氩激光光凝诱导视网膜基因表达的改变。

Argon laser photocoagulation-induced modification of gene expression in the retina.

作者信息

Wilson Ann S, Hobbs Bridget G, Shen Wei-Yong, Speed Terence P, Schmidt Uli, Begley C Glenn, Rakoczy P Elizabeth

机构信息

Department of Molecular Ophthalmology, Lions Eye Institute, The University of Western Australia, Nedlands, Australia.

出版信息

Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1426-34. doi: 10.1167/iovs.02-0622.

Abstract

PURPOSE

To generate a profile of genes expressed in the retina, RPE, and choroid after laser treatment and to identify genes that may contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases.

METHODS

Argon laser irradiation was delivered to the left eye of normal C57BL/6J mice (n = 30), with the right eye serving as the control in each animal. Three days after laser treatment, mice were culled, eyes enucleated, and the retinas dissected and pooled into respective groups. The total RNA of replicate samples was extracted, and expression profiles were obtained by microarray analysis. Data comparisons between control and treated samples were performed and statistically analyzed.

RESULTS

Data revealed that the expression of 265 known genes and expressed sequence tags (ESTs) changed after laser treatment. Of those, 25 were found to be upregulated. These genes represented a number of biological processes, including photoreceptor metabolism, synaptic function, structural proteins, and adhesion molecules. Thus angiotensin II type 2 receptor (Agtr2), a potential candidate in the inhibition of VEGF-induced angiogenesis, was upregulated, whereas potential modulators of endothelial cell function, permeability factors, and VEGF inducers, such as FGF-14, FGF-16, IL-1beta, calcitonin receptor-like receptor (CRLR), and plasminogen activator inhibitor-2 (PAI2), were downregulated.

CONCLUSIONS

In this study, genes were identified that both explain and contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. The molecular insights into the therapeutic effects of laser photocoagulation may provide a basis for future therapeutic strategies.

摘要

目的

生成激光治疗后视网膜、视网膜色素上皮(RPE)和脉络膜中表达的基因图谱,并鉴定可能有助于激光光凝治疗血管生成性视网膜疾病产生有益效果的基因。

方法

对正常C57BL/6J小鼠(n = 30)的左眼进行氩激光照射,每只动物的右眼作为对照。激光治疗三天后,处死小鼠,摘除眼球,解剖视网膜并汇集到相应组中。提取重复样本的总RNA,通过微阵列分析获得表达谱。对对照样本和处理样本进行数据比较并进行统计分析。

结果

数据显示,激光治疗后265个已知基因和表达序列标签(EST)的表达发生了变化。其中,25个基因被发现上调。这些基因代表了许多生物学过程,包括光感受器代谢、突触功能、结构蛋白和粘附分子。因此,作为抑制VEGF诱导的血管生成的潜在候选基因,血管紧张素II 2型受体(Agtr2)上调,而内皮细胞功能、通透性因子和VEGF诱导剂的潜在调节因子,如FGF-14、FGF-16、IL-1β、降钙素受体样受体(CRLR)和纤溶酶原激活物抑制剂-2(PAI2)下调。

结论

在本研究中,鉴定出了既能解释激光光凝治疗血管生成性视网膜疾病的有益效果又对其有贡献的基因。对激光光凝治疗效果的分子见解可能为未来的治疗策略提供基础。

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