Reversible Dysfunction of Retinal Ganglion Cells in Glaucoma

青光眼视网膜神经节细胞的可逆性功能障碍

• 批准号: 9053485
• 负责人: VITTORIO PORCIATTI
• 金额: $ 34.54万
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9053485
• 关键词: American; Axon; Biological Markers; Blindness; Cell Death; Cell physiology; Cessation of life; Clinical; Clinical Management; Computer software; Development; Devices; Diagnosis; Disease; Drops; Electroretinography; Environment; Failure; Functional disorder; Funding; Future; Glaucoma; Goals; Head; Health; High Prevalence; Homeostasis; Incidence; Individual; Laboratories; Measurement; Measures; Methods; Monitor; Nerve Tissue; Noise; Onset of illness; Open-Angle Glaucoma; Optic Nerve; Optical Coherence Tomography; Outcome; Patients; Pattern; Physiologic Intraocular Pressure; Population; Positioning Attribute; Posture; Predisposition; Prevalence; Process; Publications; Randomized; Recovery; Research; Retinal Ganglion Cells; Risk; Risk Factors; Services; Signal Transduction; Staging; Stress; Suspect Glaucomas; Testing; Therapeutic; Thick; Time; Tissues; Vision; Visual Fields; base; critical period; follow-up; functional loss; hemodynamics; high risk; improved; neurotrophic factor; optic nerve disorder; pressure; prevent; retinal nerve fiber layer; tool

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 and preserve vision. The objective of this study is to identify dysfunctional RGCs and the risk of their death, together with the time 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 modifiable in a critical period during which RGC electrical activity is responsive to artificial elevation/lowering of the intraocular pressure (IOP). Temporary IOP elevation with be obtained by means of head-down body posture; IOP lowering will be obtained by means of topical treatment. Our study will include 600 subjects with suspicion of glaucoma but with normal vision and visual field that will be longitudinally monitored over 4 years with state-of-the-art pattern electroretinogram (PERG), Spectral-domain Optical Coherence Tomography (SD-OCT), and other clinical measures. PERG losses result from reduced activity of viable RGCs as well as from lack of activity from dead/missing RGCs; OCT losses result from loss of RGC/axon tissue. Our specific aims will determine the risk of losing substantial RGC/axon tissue over 4 years based on baseline PERG susceptibility to head-down posture (aim1), baseline PERG abnormality (aim 2), and presence/absence of IOP-lowering treatment during follow up. Successful completion of our research will establish the notion that RGC death in glaucoma is preceded by a defined stage of modifiable RGC electrical activity, and that the risk of developing glaucoma can be predicted at baseline based on PERG. The outcome of our research will provide 1) the basis for new provocative tests of RGC functional susceptibility/reversibility using a non-invasive PERG method, 2) information needed for new methods to predict the risk of glaucoma development, 3) the time window for preventing it by timely treatment of high-risk individuals.

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死亡并保持视力。这项研究的目的是确定功能失调的RGC及其死亡的风险，以及恢复的机会之窗。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，并且在关键时期，RGC功能障碍是可修改的，在此期间，RGC电活动对人工压力（IOP）的人工升高/降低有反应。通过头向下的身体姿势获得临时IOP高程； IOP降低将通过局部处理获得。我们的研究将包括600名怀疑青光眼的受试者，但具有正常视力和视野的受试者将在4年内通过最新的图案电图（PERG）纵向监测，光谱域光学相干性层析成像（SD-OCT）将在4年内进行纵向监测。和其他临床措施。 PERG损失是由于可行的RGC的活性减少以及死亡/缺失RGC的活性而导致的； RGC/轴突组织的损失导致OCT损失。我们的具体目的将根据基线PERG对头向下姿势的敏感性（AIM1），基线PERG异常（AIM 2）（AIM 2）以及随后的情况下的存在/不存在，因此，根据基线PERG的易感性（AIM1），基线perg异常（AIM1），在关注期间的存在/不存在/不存在，我们的具体目的将在4年内损失大量RGC/轴突组织的风险。向上。成功完成我们的研究将确定一种观念，即青光眼中的RGC死亡是在定义的可修改RGC电活动的阶段，并且可以基于PERG在基线时预测患有青光眼的风险。我们研究的结果将提供1）使用非侵入性PERG方法的RGC功能敏感性/可逆性的新挑衅性测试的基础，2）2）新方法所需的信息，以预测青光眼发展的风险，3）3）通过及时治疗高风险个体来防止它。