Investigating nanoscale neuronal damages in early glaucoma towards clinical optical detection

项目摘要 我们的长期目标是开发光学相干层析成像(VIS-OCT)的新功能扩展，用于 青光眼的临床诊断和治疗。青光眼的特征是视网膜进行性丧失。 神经节细胞(RGC)和视神经缺陷和萎缩，困扰着全世界6000多万人。它是 通常发展缓慢，早期没有注意到症状和损害。照顾那些有困难的人 青光眼视力障碍给美国的医疗保健系统带来了巨大的负担。早期发现和 因此，无症状阶段的筛查技术对于更好地管理疾病至关重要。 并将产生重大的临床和经济影响。在这个提议中，超高轴向的功率 将利用分辨率(约1微米)，并通过可见光OCT提供更高的光学对比度灵敏度 (VIS-OCT)研究早期视网膜神经节细胞的光学可检测改变的机制 (RGC)对实验性青光眼小鼠模型的损伤。拟议的研究将作为以下工作的基础 目的：应用OCT对青光眼进行早期、敏感的临床诊断。首先，调查人员将确定 使用急性神经挤压损伤的小鼠模型检测RGC和轴突损伤的VIS-OCT方法。 然后，研究人员将确定VIS-OCT检测到的RGC超微结构变化的生理来源 实验性青光眼的慢性模型。最后，调查人员将确定VIS-OCT检测到的RGC 超微结构改变继续用于临床青光眼诊断的结构和功能指标 实验性青光眼的慢性模型。

Project Summary Our long-term goal is to develop new functional extensions of optical coherence tomography (vis-OCT) for clinical diagnosis and management of glaucoma. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and optic nerve defects and atrophy, afflicting more than 60 million people worldwide. It is often develops slowly with symptoms and damage that are not noticed at early stage. Caring for those with glaucomatous vision disability poses a huge burden on the US health care system. Early detection and screening techniques at asymptomatic stage is thus of critical importance for better management of the disease and will have paramount clinical and economic impacts. In this proposal, the power of the ultrahigh axial resolution (~1 µm) will be harnessed and the increased optical contrast sensitivity offered by visible-light OCT (vis-OCT) to investigate the mechanism of optically detectable alterations underlying early retinal ganglion cell (RGC) damage in mouse models of experimental glaucoma. The proposed study will serve as the foundation for objective and sensitive early clinical diagnosis of glaucoma using OCT. First, the investigators will establish vis-OCT methodology to detect RGC and axon damage using an acute mouse model of nerve crush injury. Then, the investigators will determine physiological origin of vis-OCT detected RGC ultrastructural alterations in a chronic model of experimental glaucoma. Finally, the investigators will determine that vis-OCT detected RGC ultrastructural alterations proceeds the structural and functional metrics used for clinical glaucoma diagnoses in a chronic model of experimental glaucoma.