三叉神经-下丘脑神经传导通路在眼压调控及青光眼发病中的作用及机制

青光眼是世界第一位不可逆致盲眼病，尤其是开角型青光眼发病率高、发病隐匿且早期诊断困难，因此危害极大。眼压异常波动被认为是重要危险因素，但眼压稳态维持及调控机制尚不清楚。目前认为下丘脑作为中枢神经系统关键节点，参与生理条件下眼压稳态的维持。而三叉神经作为支配眼球唯一的感觉神经在感受眼压信号及眼压信号转换中发挥举足轻重的作用。既往研究亦支持三叉神经与下丘脑间存在解剖及功能连接。因此我们提出假设：三叉神经-下丘脑神经传导通路在眼压调控以及青光眼发病中起重要作用。本项目拟通过多模态功能磁共振技术探索青光眼患者三叉神经-下丘脑神经传导通路功能连接、纤维连接以及生化代谢产物改变。并通过构建青光眼动物模型，联合逆行神经示踪、电刺激毁损及电位监测技术、免疫组化、分生技术进一步验证阐述三叉神经-下丘脑神经传导通路眼压信号传递方式以及眼压调控的生化物质基础。以期为青光眼的中枢发病机制及临床治疗新靶点提供依据。

Glaucoma is the first irreversible blind cause in the world. Open-angle glaucoma is the most harmfull due to its high incidence and latent attribute.Intraocular pressure fluctuations is regarded as one of the most prominent factors for glaucoma.However,it is still vague how the IOP remains in a steady state. Hypothalamus has previously been considered to be a key node in the control of central nervous system,which may involve in maintaining the homeostasis of intraocular pressure under physiological conditions.Trigeminal nerve regarded as the only sensory innervation of eye palys a dominant role in the receptor and transmission of the IOP signal.Previous studies have demonstrated the connective relationships betwent hypothalamus and trigeminal nerve.Therefor,this project raises a presumption: trigeminal nerve-hypothalamus pathway may play a role in the control of IOP and the pathogenesis of glaucoma.The project will make use of multi- modal functional MRI techniques to explore the functional connecions,fiber connections and neurotransmitter variation in the trigeminal-hypothalamus pathway among patients with glaucoma and ocular hypertension and normal persons.While building an animal model of glaucoma in rats , respectively, through the control of intraocular pressure and electrophysiological technologies, as well as nerve tracing and immunohistochemical methods , this project will verify further the transmission way and the biochemical bases of IOP signal. We hope to clarify the IOP mechanism of central pathways regulation and to provide a knock-down evidence for the early diagnosis of glaucoma.