低颅压是导致青光眼的重要原因之一，而视神经脑脊液淋巴回流异常是引起低颅压青光眼视神经损害的关键因素。iCOP课题组在前期工作中已经建立了猕猴和狗的青光眼实验动物模型，初步结果表明低颅压青光眼视神经损害主要是视神经蛛网膜下腔压力改变引起的压力相关性视神经损害。视神经脑脊液淋巴回流在其中具有重要作用，但具体机制目前尚不清楚。本项目拟在已建立的青光眼实验动物模型基础上，采用免疫组化和Quantum dot 655示踪等方法，揭示视神经脑脊液淋巴回流的结构基础，阐明其对视神经蛛网膜下腔压力的影响及二者之间的关系曲线。通过对比不同组别颅内压降低后颅内压与视神经蛛网膜下腔压力关系曲线的改变以及活体观察指标、组织病理学检测、轴浆流运输评估及对线粒体的影响等方法揭示青光眼视神经损害的可能机制。进一步明确低颅压及视神经脑脊液淋巴回流与“腔室效应”和视神经相关压力梯度间的关系，为建立基于损害机制的治疗提供基础

The role of low intracranial pressure (ICP) in the pathogenesis of glaucoma is more important, especially the lymphatic drainage of cerebrospinal fluid (CSF) in the optic nerve subarachnoid space (ONSAS) being fundamental for recognizing glaucoma. We have established the experimental animal model of monkey with low ICP and the CSF dynamic model of dog for research of glaucoma and identify that the glaucomatous optic neuropathy is mainly caused by the lower optic nerve subarachnoid space pressure (ONSP) which is influenced by the impaired CSF dynamics and results in the optic nerve damage. In our previous studies, we clarified the correlation between the ONSP and ICP and just in these researches, we also found that it was the lymphatic drainage of CSF around the optic nerve that is essential for understanding the glaucomatous optic neuropathy. We envisage that on the basis of our established experimental models, using Quantum dot 655 as indicator for quantitative and qualitative analyzing to identify the influences of lymphatic drainage of CSF in different levels of low ICP and effects of increasing and decreasing CSF drainage by lymphatic vessels on the ONSP as well as other methods including vivo observing items, pathological test, evaluation of axoplasmic flow and effects on mitochondrion could clarify the possible mechanism of glaucoma in order to further enrich and improve the low ICP theory and provide the theoretical and experimental basis for establishing the treatments according to the understanding of the optic nerve damage.

青光眼的致病原因不明，越来越多的临床证据表明低颅压是导致正常眼压青光眼的重要原因之一。因此，探讨颅内压与视神经蛛网膜下腔压力之间的关系以及对脑脊液循环动力学的影响对于阐明正常眼压青光眼的发病机理具有重要意义。其中，最新研究表明视神经脑脊液淋巴回流异常是引起正常眼压青光眼视神经损害的关键因素。iCOP课题组在前期工作中已经建立了低颅压猕猴实验动物模型和狗的用于青光眼脑脊液循环动力学研究实验模型，初步结果表明正常眼压青光眼视神经损害主要是视神经蛛网膜下腔压力改变引起的压力相关性视神经损害。视神经脑脊液淋巴回流在其中具有重要作用，但具体机制目前尚不清楚。本项目拟在已建立的青光眼实验动物模型基础上，结合猕猴和狗的实验模型，建立可以用于研究视神经脑脊液淋巴循环的新的模型。通过CT视神经蛛网膜下腔造影，分析时间-密度曲线，定性和定量地研究低颅压所致视神经蛛网膜下腔脑脊液循环障碍在正常眼压青光眼中的发病机制。然后，采用免疫组化和Quantum do t 655示踪等方法，揭示视神经脑脊液淋巴回流的结构基础，阐明其对视神经蛛网膜下腔压力的影响及二者之间的关系曲线。通过对比不同组别颅内压降低后颅内压与视神经蛛网膜下腔压力关系曲线，进一步明确低颅压及视神经脑脊液淋巴回流与“腔室效应”和视神经相关压力梯度间的关系，为建立基于损害机制的治疗提供基础。虽然在建立猕猴新的实验动物模型中，经反复尝试还是无法充分按照实验要求做到最小损伤地暴露视神经。但是，基于我们的实验结果，猕猴的视神经位于眼眶深部，周围有肌肉和脂肪组织，很难充分暴露，为我们的后续研究和其他研究者提供了宝贵的、可借鉴的实际经验。同时，CT视神经蛛网膜下腔造影技术可以被应用于视神经蛛网膜下腔脑脊液的循环动力学研究。