Gao Feng-Juan, Wu Ji-Hong, Li Ting-Ting, Du Shan-Shan, Wu Qiang
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai, China; Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan UniversityShanghai, China.
Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan UniversityShanghai, China; Shanghai Key Laboratory of Visual Impairment and RestorationShanghai, China; Key Laboratory of Myopia, Ministry of Health, Fudan UniversityShanghai, China.
Front Mol Neurosci. 2017 Mar 17;10:76. doi: 10.3389/fnmol.2017.00076. eCollection 2017.
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 and 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 and 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.
中脑星形胶质细胞衍生的神经营养因子（MANF）是一种新发现的分泌型神经营养因子，已被证明不仅能保护多巴胺能神经元和其他细胞类型，还能调节神经炎症和免疫反应以促进组织修复和再生。然而，迄今为止，尚无关于眼内MANF与视网膜神经节细胞（RGCs）之间关系的信息。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，我们使用[具体模型1]和[具体模型2]模型研究了MANF对RGCs的影响，并同时探索了MANF潜在的神经保护机制。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在RGCs中高表达，外源性MANF可以通过防止内质网应激介导的凋亡，在[具体模型1]和[具体模型2]中保护RGCs免受缺氧诱导的细胞损伤和凋亡。此外，在玻璃体液中可以检测到MANF，并且其浓度在病理条件下会发生变化。我们的结果提供了重要证据，表明MANF可能是一种潜在的治疗性蛋白质，可用于一系列视网膜病变的临床前阶段或诊断后，以促进RGCs的存活。玻璃体MANF可能是一种有前景的蛋白质生物标志物，用于间接评估视网膜疾病，这可以为视网膜病变提供间接证据。
