LIFE AND DEATH OF RETINAL GANGLION CELLS

视网膜神经节细胞的生与死

• 批准号: 7057225
• 负责人: VITTORIO PORCIATTI
• 金额: $ 14.79万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057225
• 关键词: cell death; cell population study; cytoprotection; disease /disorder model; disease /disorder onset; electroretinography; glaucoma; glaucoma test; intraocular pressure; laboratory mouse; longitudinal animal study; neuroprotectants; noninvasive diagnosis; optic nerve disorder; optical tomography; pathologic process; retina disorder; retinal ganglion; tissue /cell culture

DESCRIPTION (provided by applicant): Glaucoma is characterized by progressive death of retinal ganglion cells (RGCs) resulting in blindness. The long-term implication of this research is prevention of RGC dysfunction and loss in patients with glaucoma. Our objective is to define the natural history of RGC dysfunction and death in an inbred strain mouse model of glaucoma (DBA/2J) with spontaneously elevated intraocular pressure (lOP). We will use non-invasive and improved methodologies such as Pattern Electroretinogram (PERG), Optical Coherence Tomography (OCT) and non-contact tonometry, as well as an unique non-glaucomatous mouse with DBA genetic background. The central hypothesis is that there is a substantial population of dysfunctional RGCs that can be detected by state-of-the-art structural-functional comparison in a longitudinal evaluation.The rationale is that the characterization of RGC dysfunction and death in a readily available mouse model of glaucoma by means of methods adapted from human clinical examination will provide a powerful experimental system for treating and even reversing the condition in humans. We will focus on two specific aims: 1) To improve methodologies for non-invasive quantification of RGC function/number and lOP, and 2) To monitor the onset and progression of retinopathy in individual animals. The proposed research is innovative, because it is based on non-invasive and sequential monitoring of key variables in glaucoma and unique strains of mice. We are particularly prepared to undertake this study because our research team combines specific expertise in visual electrophysiology, retinal imaging, mouse glaucoma models, and biophysics. Our expectation is that we will be able to determine whether RGC dysfunction precedes RGC death, determine functional and anatomical endpoints for onset and progression, and determine the visual capabilities of surviving RGCs. Such outcomes are significant, since exploiting an animal model for testing neuroprotective strategies that preserve visual function is an important component of future research on treatments for glaucoma.

描述(申请人提供)：青光眼的特征是视网膜神经节细胞(RGC)进行性死亡导致失明。这项研究的长期意义是预防青光眼患者RGC功能障碍和丢失。我们的目标是在自发性高眼压(LOP)的近交系小鼠青光眼模型(DBA/2J)中确定RGC功能障碍和死亡的自然历史。我们将使用非侵入性和改进的方法，如模式视网膜电信号(PERG)、光学相干断层扫描(OCT)和非接触眼压测量，以及独特的具有DBA遗传背景的非青光眼小鼠。核心假设是，在纵向评估中，可以通过最先进的结构-功能比较来检测到大量功能障碍的视网膜节细胞。其基本原理是，通过采用人类临床检查的方法，在现成的青光眼小鼠模型中表征视网膜节细胞功能障碍和死亡的特征，将为治疗甚至逆转人类的这种情况提供强大的实验系统。我们将集中于两个具体目标：1)改进RGC功能/数量和LOP的非侵入性量化方法；2)监测单个动物视网膜病变的发生和发展。这项拟议的研究是创新的，因为它基于对青光眼和独特品系小鼠的关键变量的非侵入性和顺序监测。我们特别准备进行这项研究，因为我们的研究团队结合了视觉电生理学、视网膜成像、小鼠青光眼模型和生物物理学方面的特定专业知识。我们的期望是，我们将能够确定RGC功能障碍是否先于RGC死亡，确定发病和进展的功能和解剖终点，并确定存活的RGC的视觉能力。这样的结果意义重大，因为利用动物模型来测试保护视觉功能的神经保护策略是未来青光眼治疗研究的重要组成部分。