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Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

机译:缺血性损伤导致视网膜和视神经细胞外基质改变

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摘要

Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration.
机译:视网膜缺血发生在多种眼睛疾病中。血流受限会引起视网膜损伤,从而导致进行性视神经变性和视力丧失。先前的研究表明,细胞外基质(ECM)成分在复杂组织(例如视网膜和视神经)中起重要作用。它们对脱细胞和再生过程有很大影响,并代表中枢神经系统神经胶质瘢痕形成的主要候选者。然而,ECM在缺血性视网膜和视神经神经变性过程中的重要性尚不完全清楚。在这项研究中,我们分析了缺血/再灌注大鼠视网膜和视神经中细胞外糖蛋白纤连蛋白,层粘连蛋白,肌腱蛋白C和腱生蛋白R以及硫酸软骨素蛋白聚糖(CSPG)聚集蛋白聚糖,brevican和phosphacan /RPTPβ/ζ的重塑通过实时定量PCR,免疫组化和Western印迹建立模型。缺血后视网膜和视神经中的多种ECM成分失调。关于纤连蛋白,缺血后视网膜中mRNA和蛋白水平显着升高,而层粘连蛋白和腱生蛋白-C在缺血后视神经中显示出增强的免疫反应性。有趣的是,CSPG在视神经中显示出明显增加的表达水平。我们的研究表明视网膜缺血后ECM分子的动态表达,这增强了它们在神经变性过程中的调节作用。

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