Identification of Mesencephalic Astrocyte-Derived Neurotrophic Factor as a Novel Neuroprotective Factor for Retinal Ganglion Cells.
Identification of Mesencephalic Astrocyte-Derived Neurotrophic Factor as a Novel Neuroprotective Factor for Retinal Ganglion Cells.
复制标题
鉴定中脑星形胶质细胞衍生的神经营养因子作为视网膜神经节细胞的新型神经保护因子
DOI：
10.3389/fnmol.2017.00076
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Gao FJ;Wu JH;Li TT;Du SS;Wu Q
中脑星形胶质细胞源性神经营养因子（Mesencephalic astrocyte-derived neurotrophic factor，MANF）是近年来发现的一种分泌型神经营养因子，它不仅具有保护多巴胺能神经元等细胞的作用，还具有调节神经炎症和免疫反应，促进组织修复和再生的作用。然而，到目前为止，没有关于MANF和视网膜神经节细胞（RGC）之间的关系的信息。在本研究中，我们首先确定了MANF在视网膜和玻璃体中的表达。然后，我们研究了MANF对RGCs的影响，在体内和体外模型，同时探讨了潜在的神经保护机制MANF。最后，我们测量了不同视网膜病变患者玻璃体中MANF的浓度。我们证明，MANF是高表达的RGCs和外源性MANF可以保护RGCs从缺氧诱导的细胞损伤和凋亡在体外和体内通过防止内质网应激介导的凋亡。此外，MANF可以在玻璃体液中检测到，并且在病理条件下浓度发生变化。我们的研究结果提供了重要的证据，MANF可能是一种潜在的治疗蛋白，用于临床前阶段或诊断后的一系列视网膜病变，以促进RGC的存活。Vitamin MANF可能是一种很有前途的间接评估视网膜病变的蛋白质生物标志物，可以提供视网膜病变的间接证据。
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly discovered secreted neurotrophic factor, has been proven to not only protect dopaminergic neurons and other cell types but also regulate neuroinflammation and the immune response to promote tissue repair and regeneration. However, to date, there is no information regarding the relationship between MANF and retinal ganglion cells (RGCs) in the eye. In the current study, we first determined the expression of MANF in the retina and vitreous. Then, we examined the effect of MANF on RGCs using both in vivo and in vitro models and simultaneously explored the underlying neuroprotective mechanisms of MANF. Finally, we measured the concentrations of MANF in the vitreous of patients with different retinopathies. We demonstrated that MANF was highly expressed in RGCs and that exogenous MANF could protect RGCs from hypoxia-induced cell injury and apoptosis both in vitro and in vivo by preventing endoplasmic reticulum stress-mediated apoptosis. Furthermore, MANF can be detected in the vitreous humor, and the concentration changed under pathological conditions. Our results provide important evidence that MANF may be a potential therapeutic protein for a range of retinal pathologies in either the preclinical stage or after diagnosis to promote the survival of RGCs. Vitreous MANF may be a promising protein biomarker for the indirect assessment of retinal disorders, which could provide indirect evidence of retinal pathology.