Morphological and Functional Changes of Locus Coeruleus in Patients with Primary Open-Angle Glaucoma and Animal Models
Morphological and Functional Changes of Locus Coeruleus in Patients with Primary Open-Angle Glaucoma and Animal Models
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原发性开角型青光眼患者蓝斑形态及功能变化及动物模型
DOI：
10.1016/j.neuroscience.2017.12.044
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发表时间：
2017-12
期刊：
影响因子：
3.3
通讯作者：
Zhiqi Chen
中科院分区：
文献类型：
--
作者：
Yuxiang Yuan;Ying Zhu;Yinwei Song;Yin Zhao;Xiaoqin Yan;Wei Chen;Mu Li;Jieling Gong;Ketao Mu;Junming Wang;Hong Zhang;Zhiqi Chen
原发性开角型青光眼（Primary open-angle glaucoma，POAG）是导致不可逆性失明的主要原因。磁共振成像（MRI）研究报告POAG和非视觉通路改变之间的关联。蓝斑（LC）是脑内释放去甲肾上腺素的主要来源，去甲肾上腺素可通过增加房水流出量降低眼内压。本研究旨在通过POAG患者和动物模型探讨青光眼与LC的关系。静息状态下的功能性MRI使用3特斯拉MR扫描仪与八通道相控阵头部线圈，MRI数据进行了分析。采用巩膜外静脉结扎烧灼法建立大鼠慢性青光眼模型。还获得了随年龄发展青光眼的DBA/2 J小鼠。免疫组化和免疫荧光染色观察LC酪氨酸羟化酶（TH）和多巴胺β羟化酶（DβH）的表达，末端脱氧核苷酸转移酶dUTP缺口末端标记法检测细胞凋亡。与对照组相比，POAG患者LC低频波动（ALFF）幅度显著增加。LC ALFF值与杯盘比、视网膜神经纤维层厚度、视功能呈显著相关（P< 0.05）。与对照组相比，LC与额叶和岛叶之间的功能连接（FC）降低，但LC与海马旁回之间的功能连接升高。青光眼动物模型显示LC中TH和DβH表达减少，细胞凋亡增加。本研究为LC与青光眼的关系提供了新的证据。LC可能在POAG的发病机制和眼压调节中起网络作用。
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness. Magnetic resonance imaging (MRI) studies report an association between POAG and nonvisual pathway alterations. Locus coeruleus (LC) is a major source of norepinephrine released in the brain, and norepinephrine can reduce intraocular pressure via increasing aqueous outflow. This study aimed to investigate the relationship between glaucoma and the LC in patients with POAG and animal models. Resting-state functional MRI was performed using a 3-Tesla MR scanner with an eight-channel phased-array head coil, and MRI data were analyzed. A rat model of chronic glaucoma was generated by episcleral vein ligation and cauterization. DBA/2J mice that develop glaucoma with age were also acquired. Immunohistochemistry and immunofluorescence staining were used to investigate LC tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DβH) expression, as well as cell apoptosis by terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining. Patients with POAG showed significantly increased amplitude of low-frequency fluctuation (ALFF) in the LC compared with controls. LC ALFF values showed significant correlations with cup-to-disk ratio, retinal nerve fiber layer thickness, and visual function (P< 0.05). Functional connectivity (FC) between the LC and frontal and insular lobes was reduced, but elevated between the LC and parahippocampal gyrus, compared with controls. Glaucoma animal models revealed reduced expression of TH and DβH in the LC, and increased cell apoptosis. In this study, we provide novel evidence for the relationship between the LC and glaucoma. The LC may act as a network in POAG pathogenesis and intraocular pressure regulation.
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