PDF(Pubmed)
Abstract：
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
摘要：
原发性开角型青光眼（POAG）是一种进行性视神经病变，多因素病因。眼内压（IOP）升高是POAG最重要的临床可改变的危险因素。所有目前的药物都以房水动力学为目标，以降低IOP。由于一些患有POAG的患者表现出有限的治疗反应或对局部用药产生眼部和全身副作用,因此需要较新的治疗剂。POAG中IOP升高是由眼前段中转化生长因子β（TGFβ）水平升高引起的小梁网细胞和分子变化引起的。需要了解TGFβ如何影响流出途径和IOP的结构和功能变化，以开发新的针对小梁网分子病理学的青光眼疗法。在这项研究中,我们评估了TGF-β1和β2处理对培养的人原代小梁细胞中miRNA表达的影响。我们的发现是在特定的miRNA（miRNA为中心），但是鉴于miRNAs在网络中控制细胞通路和过程，还报道了miRNA作用的以途径为中心的观点.评估小梁细胞中TGFβ反应性miRNA的表达将进一步了解青光眼发病机理中涉及的重要途径和变化，并可能导致miRNA作为青光眼新治疗方式的发展。
