青光眼的病理机制一直是这种永久性致盲疾病的复杂方面,但是蛋白质组学研究在许多研究中都有助于在很大程度上阐明它。这项研究旨在评估表达并了解在人房水(hAH)中鉴定出的两个新标志物(ligatin和fibulin-7)与青光眼进展有关的功能。与非青光眼对照(NG-Ctrls)相比,青光眼hAH的蛋白质含量显着增加。Ligatin,在原发性开角型青光眼(POAG)的hAH中发现了fibulin-7及其蛋白水解,原发性闭角型青光眼(PACG)和NG-Ctrls。定量证实在表达的配体没有显著差异,与NG-Ctrls和POAG相比,PACG的hAH中fibulin-7显着(P<0.05)低。重要的是,两者的免疫组织化学测定均表明它们可能参与体内TM适当结构的维持。由于氧化应激是青光眼发病的主要因素,细胞核和细胞质部分的体外分析表明,在氧化损伤人小梁网(TM)细胞后,配体的定位和表达发生了细胞内变化。而腓骨蛋白-7表达没有发现这样的变化。免疫细胞化学测定法也证实了这一点。虽然一项样本量很小的研究,这是第一份证实hAH中存在ligatin和fibulin-7的报告,量化它们的差异表达,并指出了他们参与TM结构维护的可能性。
The pathological mechanism underlying glaucoma has always been a complex aspect of this permanently blinding disease but proteomic studies have been helpful in elucidating it to a great extent in several studies. This study was designed to evaluate the expression and to get an idea about the function of two novel markers (
ligatin and fibulin-7) identified in human aqueous humor (hAH) in relation to glaucomatous progression. A significant increase in the protein content of glaucomatous hAH compared to that of non-glaucomatous controls (NG-Ctrls) was observed.
Ligatin, fibulin-7, and its proteolysis were revealed in hAH of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG) and NG-Ctrls. Quantification confirmed no significant difference in expression of
ligatin, whereas fibulin-7 was significantly (P < 0.05) low in hAH of PACG in comparison to NG-Ctrls and POAG. Importantly the immunohistochemical assay for both indicated their possible involvement in the maintenance of the appropriate structure of TM in vivo. Since oxidative stress is a major contributor to glaucomatous pathogenesis, in vitro analysis of nuclear and cytoplasmic fractions indicated intracellular changes in localization and expression of
ligatin upon oxidative insult of human trabecular meshwork (TM) cells. While no such changes were found for fibulin-7 expression. This was also corroborated with the immunocytochemical assay. Though a study with a small sample size, this is the first report which confirms the presence of
ligatin and fibulin-7 in hAH, quantified their differential expression, and indicated the possibility of their involvement in the maintenance of the TM structure.