Reversible Ganglion Cell Dysfunction in Glaucoma

青光眼可逆性神经节细胞功能障碍

• 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
• 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

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：青光眼视神经病变的失明是由于视网膜神经节细胞(RGC)的死亡。我们的长期目标是挽救功能失调的视网膜节细胞，以防止青光眼早期的细胞死亡。本研究的目的是明确RGC功能障碍与引起的眼压变化的关系，以及RGC功能障碍与死亡之间的关系。我们的中心假设是，RGC功能障碍发生在RGC死亡之前，并可以通过降低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的专家。我们的临床环境中有一个独特的大量青光眼患者和老年患者，由于非裔美国人和西班牙裔种族，青光眼的风险增加。其具体目的是1)检验RGC功能障碍是由LOP引起并可通过降低LOP逆转的假说，2)检验在青光眼进展的任何给定时间RGC功能障碍大于RGC损失的假说。RGC丢失和存活的RGC功能障碍将用图形视网膜电信号(PERG)测量，而RGC的解剖丢失将用光学相干断层扫描(Oct3)测量。这两种方法都进行了优化，以探测同等数量的具有类似灵敏度的神经元。初步结果表明，降低LOP可以改善PERG缺陷，临时增加LOP会加剧PERG缺陷，并且PERG损失相对大于OCT损失，这一假说得到支持。这一结合的创新方法将更好地理解青光眼进展过程中的病理生理机制。这项研究有望为青光眼的早期治疗或预防提供理论依据，并将开发一种基于PERG改善程度来监测治疗效果的方法。由于青光眼致盲人数随着寿命的延长而稳步增加，这些结果有望对减轻我国的医疗负担产生巨大的潜在影响。