Schlemm's管作为自主神经调控靶点的研究

Our previous study shows that central nervous system (CNS) participates in the pathogenesis of POAG. To definite the effect target and the mechanism in the eye is the key to optimize the theory of CNS involving in the pathogenesis of POAG. Schlemm's Canal (SC) is a major part of aqueous outflow pathway and the key position of affecting the intraocular pressure (IOP), which has been confirmed in recent studies that the opening and closing statue is associated with IOP. Our previous study also found that only a fraction of the SC is actively involved in aqueous humor drainage; the excitement of autonomic nervous such as doing exercises expands SC,descending the IOP; autonomic nerve projection exists in the SC area, prompting that autonomic nervous may participate in SC regulation. Therefore we hypothesize that SC is projected by the hypothalamus, being vital importance effect target in central IOP regulation that its opening and closing states is regulated by the autonomic nerve to affects the intraocular pressure ,which is an important factor in the onset of POAG. This study will firstly use the means of neural tracer and immunofluorescence to clear the location of SC autonomic nervous, as well as its quantity and characteristics,further confirmed the action and the efficiency of autonomic nervous regulation in SC by observing the status of it through 7T MRI after blocking the pterygopalatine ganglion and the superior cervical ganglion ,and lastly detecting the correlation between the opening and closing state of SC and intraocular pressure changes with drug intervention and by adjusting the autonomic nervous system—finally provide new experimental basis for the central mechanism of POAG.

前期研究显示POAG发病有中枢因素参与。明确眼部中枢调控的效应靶点与机制是完善中枢参与POAG发病学说的关键。Schlemm’s Canal（SC）是房水排出主要通路和影响眼压的关键部位，其开合状态与眼压相关。我们研究发现：正常情况下SC呈节段性开放；兴奋自主神经，可使SC扩张，眼压下降；SC有自主神经投射，提示SC开合可能受自主神经调控。假设：SC接受下丘脑自主神经投射，是眼压调控的重要效应靶点，自主神经通过调节SC开合状态，影响房水排出，参与POAG发病。本项目将利用神经示踪、免疫荧光手段明确SC自主神经投射部位、数量与性质；刺激和阻断效应通路不同节点，用7T磁共振评估房水排出速率，判断SC开合状态与眼压变化关系，证实自主神经调节SC效应动作和效率；用工具药调节自主神经，观察POAG患者SC开合状态与眼压变化关系。为POAG发病的中枢机制提供理论和实验依据。

国内外青光眼团队近年来共同提出中枢调控参与POAG发病，但中枢调控POAG发病的效应靶点与机制不明确。研究团队在前期基础上，在本项目中重点关注了Schlemm's Canal（SC）。SC是主要的房水排出通道，其开合与眼压变化相关。本项目利用POAG队列-动物模型-细胞模型，探讨了SC受自主神经调节的可能性及其相关机制，具体发现如下：①，人房角组织受自主神经的调控；②，POAG患者眼压调控的关键点在SC，与正常人相比，POAG患者的整体自主神经功能可发生紊乱；③，大鼠的TM-SC受到自主神经活动的调节；④，副交感神经递质VIP对眼压有保护作用。该研究为阐明中枢调控POAG发病提供了新的研究靶点，即SC受自主神经调控，副交感神经递质VIP潜在具有降低眼压的可能。本研究为进一步的POAG分子治疗提供了新的研究策略与干预靶点。