LIFE AND DEATH OF RETINAL GANGLION CELLS

视网膜神经节细胞的生与死

• 批准号: 6846493
• 负责人: VITTORIO PORCIATTI
• 金额: $ 15.15万
• 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/6846493
• 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（由申请人提供）：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。这项研究的长期影响是预防青光眼患者的RGC功能障碍和损失。 我们的目标是在具有自发升高的眼内压（LOP）的青春期菌株小鼠模型（DBA/2J）中定义RGC功能障碍和死亡的自然史。我们将使用非侵入性和改进的方法，例如模式电图（PERG），光学相干断层扫描（OCT）和非接触式tonometry，以及具有DBA遗传背景的独特的非闪瘤小鼠。 中心假设是，在纵向评估中，可以通过最新的结构功能比较来检测到大量功能失调的RGC。通过根据人类临床检查改编的方法的青光眼模型将提供一个强大的实验系统，用于治疗人类状况。我们将重点关注两个具体目标：1）改善对RGC功能/数量和LOP的非侵入性定量方法的方法，以及2）监测单个动物视网膜病变的发作和进展。拟议的研究具有创新性，因为它基于对青光眼和独特小鼠菌株中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，确定发作和进展的功能和解剖终点，并确定存活的RGC的视觉能力。 这样的结果很重要，因为利用动物模型来测试保留视觉功能的神经保护策略是青光眼治疗方法的未来研究的重要组成部分。