REVERSIBLE GANGLION CELL DYSFUNCTION IN GLAUCOMA

青光眼可逆性神经节细胞功能障碍

• 批准号: 8197370
• 负责人: VITTORIO PORCIATTI
• 金额: $ 36.35万
• 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 2013-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197370
• 关键词: Address; Adverse effects; African American; American; Axon; Beds; Biological Markers; Biometry; Biophysics; Blindness; Cell Death; Cell physiology; Cessation of life; Clinical; Clinical Management; Cross-Sectional Studies; Data; Deterioration; Disease; Drops; Electrophysiology (science); Electroretinography; Ethnic Origin; Exposure to; Eye; Functional disorder; Funding; Future; Glaucoma; Goals; Hispanics; Homeostasis; Image; Individual; Letters; Longevity; Longitudinal Studies; Measurement; Measures; Metabolic; Metabolism; Modeling; Names; National Eye Institute; Natural History; Neuropathy; Ophthalmology; Optical Coherence Tomography; Outcome; Patients; Pattern; Photic Stimulation; Physiologic Intraocular Pressure; Population; Predisposition; Prevalence; Prevention; Principal Investigator; Quality of life; Recovery; Research; Retinal; Retinal Ganglion Cells; Risk; Severities; Staging; Stress; Structure; Structure-Activity Relationship; Suspect Glaucomas; Time; Vision research; Visual; alternative treatment; body position; carboxyl radical; cohort; cost effective; ganglion cell; high risk; improved; innovation; loss of function; older patient; pressure; prevent; programs; response; visual stimulus

DESCRIPTION (provided by applicant): Glaucoma causes progressive damage and death of retinal ganglion cells (RGCs) resulting in blindness. The prevalence of the disease will rise to a projected 3 million Americans by 2020. Our long-term goal is to prevent RGC death in the early stages of glaucoma. The objective of this study is to identify dysfunctioning RGCs and the window of opportunity for their recovery. Our central hypothesis is that RGCs undergo a stage of reversible dysfunction before dying, and that RGC dysfunction is due to impaired tolerance to intraocular pressure (IOP). Our study will include at least 500 subjects at increased risk of having or developing glaucoma and at least 100 normal controls. Our specific aims are 1) to identify dysfunctional RGCs and evaluate their lifespan, thereby extending the longitudinal study initiated in 2004, 2) to characterize the tolerance of RGC function to both IOP increase and metabolic challenge, and 3) to validate measurements of RGC dysfunction as biomarkers to predict severity of future functional and structural loss. We will use the Pattern Electroretinogram (PERG) and Optical Coherence Tomography (OCT) as non-invasive surrogate measures of RGC function and RGC axon number, respectively. PERG losses result from both reduced activity of viable RGCs and lack of activity of dead RGCs. OCT losses result from lack of axons of dead RGCs. The central hypothesis is supported by our previous results showing that in early glaucoma PERG deficits are relatively larger than OCT deficits, and may be improved by IOP-lowering treatment. Preliminary data show that PERG deficits may be temporarily induced by either IOP elevation obtained with change in body position or by prolonged exposure to metabolically challenging visual stimuli. The rationale is that this innovative approach will provide a set of functional biomarkers to detect susceptibility of RGCs and predict their fate. This outcome will have high significance on identifying individuals at high-risk of developing glaucoma damage and determining the necessity of treatment. Our research team includes experts in glaucoma, visual electrophysiology, retinal imaging, biophysics, and biostatistics. 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 electrical activity of retinal ganglion cells non-invasively measured by pattern electroretinogram over time may be altered in subjects suspected of having glaucoma, or may become temporarily altered in response to a non-invasive stress occurring when the eye pressure is increased by lying on a bed, or the retinal metabolism is accelerated by staring at a contrasted image. These functional biomarkers have great relevance for clinical management of the disease in order to predict future severity of progression, determine the necessity of pressure-lowering treatment, make prevention a cost-effective measure, and limit the impact of side effects and deterioration of quality of life.

描述（由申请人提供）：青光眼会导致视网膜神经节细胞（RGC）的进行性损害和死亡，导致失明。该疾病的患病率将到2020年预计300万美国人。我们的长期目标是防止青光眼初期RGC死亡。这项研究的目的是确定RGC功能障碍和恢复机会窗口。我们的中心假设是，RGC在死亡前会经历可逆功能障碍的阶段，并且RGC功能障碍是由于对眼内压（IOP）的耐受性受损所致。我们的研究将包括至少500名患有或发展青光眼的风险和至少100个正常对照的受试者。我们的具体目的是1）确定功能失调的RGC并评估其寿命，从而扩展了2004年启动的纵向研究，2）表征RGC功能对IOP增加和代谢挑战的耐受性，以及3），以验证RGC功能障碍的测量结果作为预测未来功能和结构损失严重程度的生物标志物。我们将分别将图案电图（PERG）和光学相干断层扫描（OCT）用作RGC功能和RGC轴突数的非侵入性替代测量。 PERG损失均由降低可行的RGC的活性和死亡RGC的活性。十月损失是由于缺乏死亡RGC的轴突而导致的。我们先前的结果表明，在早期的青光眼缺陷中，perg缺损相对较大，并且可以通过降低IOP治疗来改善中心假设。初步数据表明，PERG缺陷可能是由于身体位置变化而获得的IOP升高或长时间暴露于代谢上具有挑战性的视觉刺激而暂时引起的。理由是，这种创新的方法将提供一组功能性生物标志物来检测RGC的敏感性并预测其命运。该结果将对确定高风险发展青光眼损害的人具有很高的意义，并确定治疗的必要性。我们的研究团队包括青光眼，视觉电生理学，视网膜成像，生物物理学和生物统计学专家。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。在怀疑患有青光眼的受试者中，通过模式电图随着时间的时间测量的视网膜神经节细胞的电活动可能会改变，或者可能会因躺在A上增加眼压而增加的非侵入性应力而暂时改变。床，或视网膜代谢通过盯着对比图像加速。这些功能性生物标志物与该疾病的临床管理具有很大的相关性，以预测未来的进展严重程度，确定降压压力治疗的必要性，使预防成为具有成本效益的措施，并限制了副作用的影响和副作用的影响和质量的质量生活。