Abstract：
Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.
摘要：
尽管小梁网（TM）的生物力学变化对糖皮质激素诱导的高眼压（GC-OHT）的发病机理很重要，它发展的潜在分子机制存在知识空白。在这项研究中,我们对3只恒河猴的一只眼睛进行了玻璃体内注射曲安奈德（IVTA）。IVTA之后,我们使用原子力显微镜评估了TM硬度，并研究了蛋白质组和miRNA表达谱的变化。与未注射的对照眼相比，3只猕猴中的一只发生了GC-OHT，眼压差异为4.2mmHg，TM较硬，弹性模量平均增加0.60kPa。在IVTA治疗的眼睛中，与细胞外基质重塑相关的蛋白质，细胞骨架重排,线粒体氧化还原显著上调。IVTA后显著上调的miR-29b和下调的miR-335-5p支持氧化应激和线粒体自噬在GC介导的TM生物力学变化中的作用。分别。IVTA后miR-15/16簇的显著上调可能表明导致流出阻力增加的TM细胞凋亡。尽管样本量很小，这些结果扩展了我们对TM中GC介导的反应的认识，此外，可能有助于解释临床环境中的类固醇反应性。
