Investigating nanoscale neuronal damages in early glaucoma towards clinical optical detection

研究早期青光眼的纳米级神经元损伤以进行临床光学检测

• 批准号: 10228558
• 负责人: Xiaorong Liu
• 金额: $ 50.75万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228558
• 关键词: Acute; Anatomy; Animal Model; Animals; Atrophic; Axon; Behavior; Biological Markers; Blindness; Caring; Cell Death; Cell Density; Cell Survival; Cessation of life; Chronic; Clinical; Clinical Management; Contrast Sensitivity; Crush Injury; Defect; Dendrites; Detection; Diagnosis; Disease Management; Early Diagnosis; Electroretinography; Exhibits; Experimental Models; Foundations; Glaucoma; Goals; Healthcare Systems; Human; Image; Imaging technology; Individual; Investigation; Label; Left; Length; Light; Measures; Methodology; Modeling; Molecular; Monitor; Mus; Nerve Crush; Neurons; Optic Nerve; Optic Nerve Injuries; Optical Coherence Tomography; Optics; Patient imaging; Patients; Phenotype; Physiologic Intraocular Pressure; Physiological; Property; Reporter; Research Personnel; Resolution; Retina; Retinal Ganglion Cells; Risk; Structure; Symptoms; System; Techniques; Technology; Thick; Thinness; Time; Transgenic Mice; Translating; Visible Radiation; Vision; Vision Disorders; Visual; Work; axon injury; cell injury; clinical Diagnosis; clinical application; clinical imaging; contrast imaging; design; early screening; economic impact; fundus imaging; human model; imaging modality; improved; in vivo; medical attention; mouse model; nanoscale; neuronal cell body; operation; retinal nerve fiber layer; technology development; technology validation; tool

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.

项目摘要 我们的长期目标是开发光学相干断层扫描（vis-OCT）的新功能扩展， 青光眼的临床诊断和治疗。青光眼的特征是视网膜色素的进行性丧失。 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。是 通常发展缓慢，症状和损害在早期阶段没有注意到。照顾那些 昏迷性视力残疾对美国医疗保健系统构成巨大负担。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 并且将具有重要的临床和经济影响。在这个提议中， 分辨率（~1 µm）将被利用，可见光OCT提供的光学对比灵敏度增加 （vis-OCT）以研究早期视网膜神经节细胞的光学可检测改变的机制 (RGC)小鼠实验性青光眼模型的损害。拟议的研究将作为以下方面的基础： 使用OCT对青光眼进行客观而敏感的早期临床诊断。首先，研究人员将建立 vis-OCT方法使用神经挤压损伤的急性小鼠模型检测RGC和轴突损伤。 然后，研究人员将确定vis-OCT检测到的RGC超微结构改变的生理起源， 实验性青光眼的慢性模型。最后，研究人员将确定vis-OCT检测到RGC 超微结构的改变进行了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。

项目成果

Characterization of retinal ganglion cell damage at single axon bundle level in mice by visible-light optical coherence tomography fibergraphy.

• DOI: 10.4103/1673-5374.343906
• 发表时间: 2023-01
• 期刊: NEURAL REGENERATION RESEARCH
• 影响因子: 6.1
• 作者: Liu, Xiaorong;Zhang, Hao F.
• 通讯作者: Zhang, Hao F.

Symmetrically dispersed spectroscopic single-molecule localization microscopy

• DOI: 10.1038/s41377-020-0333-9
• 发表时间: 2020-05-25
• 期刊: LIGHT-SCIENCE & APPLICATIONS
• 影响因子: 19.4
• 作者: Song, Ki-Hee;Zhang, Yang;Zhang, Hao F.
• 通讯作者: Zhang, Hao F.

RainbowSTORM: an open-source ImageJ plug-in for spectroscopic single-molecule localization microscopy (sSMLM) data analysis and image reconstruction

• DOI: 10.1093/bioinformatics/btaa635
• 发表时间: 2020-10-01
• 期刊: BIOINFORMATICS
• 影响因子: 5.8
• 作者: Davis, Janel L.;Soetikno, Brian;Zhang, Hao F.
• 通讯作者: Zhang, Hao F.

Far-Red Photoactivatable BODIPYs for the Super-Resolution Imaging of Live Cells.

• DOI: 10.1021/jacs.8b09099
• 发表时间: 2018-10-10
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Zhang, Yang;Song, Ki-Hee;Tang, Sicheng;Ravelo, Laura;Cusido, Janet;Sun, Cheng;Zhang, Hao F.;Raymo, Francisco M.
• 通讯作者: Raymo, Francisco M.

High-Throughput Single-Molecule Spectroscopy Resolves the Conformational Isomers of BODIPY Chromophores

• DOI: 10.1021/acs.jpclett.9b02250
• 发表时间: 2019-11-07
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
• 影响因子: 5.7
• 作者: Sansalone, Lorenzo;Zhang, Yang;Raymo, Francisco M.
• 通讯作者: Raymo, Francisco M.