Reversible Ganglion Cell Dysfunction in Glaucoma

青光眼可逆性神经节细胞功能障碍

基本信息

批准号：
7171829
负责人：
VITTORIO PORCIATTI
金额：
$ 29.42万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-12-01 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7171829
关键词：
African American Anatomy Biophysics Blindness Cell Count Cell Death Cell physiology Cells Cessation of life Clinical Condition Country Cross-Sectional Studies Dependence Depth Deterioration Early treatment Electrophysiology (science)Electroretinography Elevation Enrollment Equation Ethnic Origin Functional disorder Ganglion Cell Layer Glaucoma Goals Healthcare Hispanics Image Longevity Longitudinal Studies Measures Medical Methods Modeling Monitor Nerve Fibers Neurons Neuropathy Noise Numbers Optic Nerve Optical Coherence Tomography Patients Pattern Physiologic Intraocular Pressure Population Prevention Rate Recovery Research Research Personnel Retinal Retinal Ganglion Cells Risk Scotoma Signal Transduction Staging Structure-Activity Relationship Suction Testing Thick Time Treatment Efficacy Vision Visual base care burden expectation functional loss ganglion cell improved innovation neuroprotection older patient optic nerve disorder pressure prevent programs response

项目摘要

DESCRIPTION: Loss of sight in glaucomatous optic neuropathy is due to the death of retinal ganglion cells (RGCs). Our long-term goal is to rescue dysfunctioning RGCs to prevent cell death in the early stages of glaucoma. The objective of this study is to define the relationship between RGC dysfunction and induced changes of the intraocular pressure (lOP), and that between RGC dysfunction and death over time. Our central hypothesis is that RGC dysfunction precedes RGC death and can be reversed by lowering the lOP. Our research team includes experts in glaucoma, visual electrophysiology, retinal imaging, and biophysics. Our clinical setting has a uniquely large population of glaucoma patients and older subjects at increased risk of glaucoma due to African-American and Hispanic ethnicity. The specific aims are 1) to test the hypothesis that RGC dysfunction is caused by lOP and can be reversed by lowering lOP, and 2) to test the hypothesis that RGC dysfunction is larger than RGC loss at any given time in the progression of glaucoma. Functional losses resulting from both RGC loss and dysfunction of viable RGCs will be measured with the pattern electroretinogram (PERG), and anatomic loss of RGCs will be measured with Optical Coherence Tomography (OCT3). Both measures are optimized to probe an equivalent number of neurons with comparable sensitivity. Hypotheses are supported by preliminary results showing that PERG deficits are improved by lOP-lowering treatments, and exacerbated by temporary lOP increases, and that PERG losses are relatively larger than OCT losses. This combined, innovative approach will yield a better understanding of the pathophysiological mechanisms involved in the progression of glaucoma. It is expected that this research will provide a rationale for the early treatment or prevention of glaucoma, and will develop a method to monitor the efficacy of treatment based on the amount of PERG improvement. Since blindness from glaucoma is steadily growing with increasing longevity, these results are expected to have a high potential impact on alleviating the health care burden in our country.

描述：青光眼视觉神经病的视力丧失是由于视网膜神经节细胞（RGC）死亡所致。我们的长期目标是营救功能障碍的RGC，以防止青光眼初期的细胞死亡。这项研究的目的是定义RGC功能障碍与眼内压（LOP）变化之间的关系，以及随着时间的推移RGC功能障碍与死亡之间的关系。我们的中心假设是RGC功能障碍先于RGC死亡，可以通过降低LOP来逆转。我们的研究团队包括青光眼，视觉电生理学，视网膜成像和生物物理学专家。我们的临床环境具有众多的青光眼患者和较老的受试者，由于非裔美国人和西班牙裔种族而导致青光眼风险增加。具体目的是1）测试RGC功能障碍是由LOP引起的假设，并且可以通过降低LOP逆转，以及2）检验以下假设：RGC功能障碍在gla糖瘤进展的任何给定时间都大于RGC损失。通过模式电图（PERG），将测量RGC损耗和可行RGC功能障碍造成的功能损失，并将用光学相干断层扫描（OCT3）测量RGC的解剖学损失。两种措施均已优化以探测具有可比灵敏度的同等数量的神经元。初步结果支持假设，表明PERG缺陷通过降低LOP的处理得到改善，并因临时LOP增加而加剧，并且PERG损失相对较大，大于OCT损失。这种结合的创新方法将更好地理解青光眼发展所涉及的病理生理机制。预计这项研究将为早期治疗或预防青光眼提供基本原理，并将开发一种根据PERG改善量监测治疗功效的方法。由于青光眼的失明随着寿命的增加而稳步增长，预计这些结果将对减轻我国的医疗保健负担产生很大的潜在影响。