Structure-Function of the Retina With Neuroprotection

视网膜的结构-功能与神经保护

基本信息

批准号：
7922971
负责人：
ARTHUR J WEBER
金额：
$ 22.96万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-12-01 至 2011-03-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7922971
关键词：
Address Affect Animals Ants Appearance Area Axon Axonal Transport Biochemical Biological Preservation Blood Vessels Brain-Derived Neurotrophic Factor Cannulations Cell Count Cell Nucleus Cell Survival Characteristics Chronic Confocal Microscopy Data Disease Dorsal Eye Felis catus Glaucoma Goals Grant Histological Techniques Histology Image Analysis Injection of therapeutic agent Injury Knowledge Label Lateral Geniculate Body Life Measurement Mechanics Methods Modeling Morphology Nerve Nerve Crush Nerve Degeneration Neurons Neuropathy Neuroprotective Agents Optic Disk Optic Nerve Optic Nerve Injuries Pattern Pharmaceutical Preparations Photic Stimulation Physiologic Intraocular Pressure Preparation Primates Procedures Process Property Rattus Retina Retinal Retinal Degeneration Retinal Ganglion Cells Scotoma Staining method Stains Structure Techniques Testing Thalamic structure Therapeutic Visual Visual Cortex Visual Pathways Visual evoked cortical potential Visual system structure Work base density direct application ganglion cell injured nerve injury neuroprotection neurotrophic factor osmotic minipump pressure research study response retinal nerve fiber layer treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Glaucoma is a disease of the visual system often characterized by pressure-induced damage to the optic nerve. This results not only in a loss of ganglion cells from the retina, but also degeneration of their target neurons in the lateral geniculate nucleus (LGN) of the thalamus. While numerous studies have shown that direct application of neurotrophic factors to the eye can reduce ganglion cell loss following optic nerve injury, an important issue that has not been addressed is whether 'rescued' neurons retain their normal structural and functional properties, and thus were worth saving. The first specific aim of this proposal is to compare the morphologies and visual response properties of ganglion cells from normal eyes with those from eyes that have received either an optic nerve injury alone, or nerve injury combined with intraocular treatment of brain-derived neurotrophic factor (BDNF), a potent neuroprotectant in the eye. The basic mechanism underlying the progressive neuropathy that characterizes glaucoma is thought to be a reduction in the level of trophic material retinal ganglion cells receive from their target neurons in the LGN due to the nerve injury. This results not only from pressure-induced blockage of axonal transport within the nerve, but also the progressive loss of target neurons, and thus trophic factor levels, within the LGN itself. At present, however, no data are available concerning the extent to which treatment beyond the eye might enhance and/or prolong ganglion cell survival compared with treatment of the eye alone. The second specific aim of this study will examine the neuroprotective effects that application of BDNF to both the eye and thalamus has on retinal ganglion cell and LGN neuron survival following different durations post nerve injury. In all cases, the structural and functional integrity of the retina, as well as the entire central visual pathway, will be assessed using non-invasive electroretinographic and visual evoked methods, and with intracellular recording and labeling of single ganglion cells using our isolated, living retina, preparation. The proposed studies represent a continuation of our previous work concerning optic nerve injury and retinal ganglion cell degeneration. They will provide new and important information concerning the functional integrity of ganglion cells following trophic factor-based rescue, and they will advance our understanding of the extent to which new treatment strategies for long-term ganglion cell survival and central visual pathway stability also should include treatment beyond the eye itself.

描述（由申请人提供）：青光眼是视觉系统的一种疾病，通常以压力引起的视神经损害。这不仅导致了来自视网膜的神经节细胞的丧失，还导致其靶神经元在丘脑的侧向基因核（LGN）中的变性。尽管大量研究表明，神经营养因子在眼睛上的直接应用可以减少神经神经损伤后的神经节细胞损失，但尚未解决的一个重要问题是“救出”神经元是否保留其正常的结构和功能特性，因此值得节省。该提案的第一个具体目的是比较正常眼睛的神经节细胞的形态和视觉反应特性与单独接受视神经损伤的眼睛的神经节细胞的形态和视觉反应特性，或者是眼睛衍生的神经营养因子（BDNF）的神经损伤，是眼中有效的神经保护剂的神经损伤。特征是青光眼的进行性神经病变的基本机制被认为是由于神经损伤而从LGN的靶神经元中获得的营养材料视网膜神经节细胞水平的降低。这不仅是由于在LGN本身内部的轴突转运所引起的压力诱导的轴突转运的阻塞，还来自于靶神经元的进行性丧失，从而逐渐丧失营养因子水平。然而，目前，与单独的眼睛的治疗相比，目前尚无有关眼睛以外的治疗可能增强和/或延长神经节细胞存活程度的数据。这项研究的第二个具体目的将研究神经保护作用，即在神经损伤后不同持续时间后，BDNF在视网膜神经节细胞和LGN神经元存活中的应用对视网膜神经节细胞和LGN神经元的生存。在所有情况下，视网膜的结构和功能完整性以及整个中央视觉途径都将使用非侵入性电子图和视觉诱发方法评估，并使用我们的隔离，活的视网膜进行准备，并使用单个神经节细胞的细胞内记录和标记。拟议的研究代表了我们先前关于视神经损伤和视网膜神经节细胞变性的工作的延续。他们将提供有关基于营养因子的救援后神经节细胞功能完整性的新的重要信息，并将提高我们对长期神经节细胞存活和中央视觉途径稳定性的新治疗策略在多大程度上的理解。