Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve.
Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve.
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中脑星形胶质细胞源性神经营养因子在视网膜和视神经中的表达和分布
DOI：
10.3389/fnhum.2016.00686
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发表时间：
2016
影响因子：
2.9
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Gao FJ;Zhang SH;Li TT;Wu JH;Wu Q
中脑星形胶质细胞衍生神经营养因子（MANF），也被称为Arginine-Rich， Mutated in early stage Tumors (ARMET)，是一种分泌性内质网应激（ERS）蛋白，在哺乳动物组织中广泛表达。迄今为止，对MANF在视网膜和视神经（ON）中的分布和表达知之甚少。因此，我们采用实时荧光PCR、免疫荧光染色和western blotting等方法研究了MANF在ON和视网膜中的表达和分布。大鼠和小鼠在视网膜上的结果高度一致。在大鼠的两种组织中均检测到MANF，其中主要定位于神经节细胞层（GCL），其次是内核层（INL）。大鼠视网膜中的MANF蛋白水平比ON高3.33倍。此外，人视网膜的视网膜神经节细胞（RGCs）强烈表达MANF。在人类ON中，MANF与胶质纤维酸性蛋白（GFAP）部分共定位，表明它并不局限于星形胶质细胞。体外研究证实，MANF可以在RGCs中强烈表达，并且主要存在于细胞质中。随着时间的推移，缺氧可以刺激MANF表达上调，提示MANF在健康和疾病中都可能在RGCs的功能调节中发挥重要作用。我们认为，本研究提高了我们对MANF在视网膜和ON中的分布和表达的认识，有助于进一步分析其与相关眼科疾病的相互作用和相关性。
Mesencephalic astrocyte-derived neurotrophic factor (MANF), otherwise named Arginine-Rich, Mutated in Early-stage Tumors (ARMET), is a secretory endoplasmic reticulum stress (ERS) protein that is widely expressed in mammalian tissues. To date, little is known about the distribution and expression of MANF in the retina and optic nerve (ON). Therefore, we studied the expression and distribution of MANF in the ON and retina by real-time PCR, immunofluorescence staining and western blotting. Results from rat and mouse were highly consistent in the retina. MANF was detected in both tissues in rat, wherein it was principally localized to the ganglion cell layer (GCL), followed by the inner nuclear layer (INL). The MANF protein levels in the rat retina were 3.33-fold higher than in the rat ON. Additionally, MANF was robustly expressed by retinal ganglion cells (RGCs) in the human retina. In human ON, MANF was partially co-localized with glial fibrillary acidic protein (GFAP), suggesting that it was not restricted to astrocytes. In vitro studies confirmed that MANF could be robustly expressed in RGCs and was found principally within the cytoplasm. Hypoxia can stimulate up-regulation by of MANF expression over time, suggesting that MANF may play a vital role in the functional regulation of RGCs both in health and disease. We believe that the present study improves our understanding of the distribution and expression of MANF in the retina and ON and could help in further analysis of its interact and correlate with the relevant ophthalmic diseases.