Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration
Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration
复制标题
神经退行性青光眼患者血浆 Drebrin 水平升高
DOI：
10.3389/fnins.2019.00326
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发表时间：
2019-04-03
影响因子：
4.3
通讯作者：
Chi, Zai-Long
中科院分区：
文献类型：
--
作者：
Gan, Yi-Jing;Fang, Ai-Wu;Chi, Zai-Long
青光眼是一种以视网膜神经节细胞（RGC）进行性变性为特征的视神经病变。几种细胞骨架蛋白（如tau蛋白）的异常与神经退行性疾病的发病机制有关，可能是青光眼进展的起始因素，并发生在轴突变性之前。发育调节脑蛋白（Dreplastin或DBN 1）是一种进化上保守的肌动蛋白结合蛋白，在神经元中发挥重要作用，并与神经退行性疾病有关。然而，青光眼患者中循环DBN 1水平与RGC变性之间的关系仍不清楚。在我们的初步研究中，我们使用蛋白质组学分析来检测青光眼患者血浆中的drexin蛋白。随后，我们共招募了232例患者，包括原发性闭角型青光眼（PACG），原发性开角型青光眼（POAG）和Posner-Schlossman综合征（PS），并测量其DBN 1血浆水平。我们观察到原发性青光眼患者的DBN 1血浆水平升高，但与非轴突病对照组相比，PS患者的DBN 1血浆水平未升高。有趣的是，与所有患者组中tau血浆水平增加相反，青光眼患者中升高的dreplasma水平与视网膜神经纤维层缺陷（RNFLD）相关。为了进一步探讨DBN 1在神经退行性变中的表达，我们进行了视神经挤压（optic nerve crush，ONC）模型的实验，观察到DBN 1在血清和视网膜中的表达增加，在ONC后下降。这一结果加强了神经变性青光眼患者循环DBN 1水平升高的可能性。总之，我们的研究结果表明，循环DBN 1水平与RNFLD相关，并可能反映青光眼患者RGCs损伤的严重程度。联合测量循环dreplatin和tau水平可能是监测神经退行性疾病进展的有用指标。
Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.