RETINOPETAL AXONS OF MAMMALIAN RETINAS

哺乳动物视网膜的视网膜轴突

• 批准号: 7349881
• 负责人: DAVID W MARSHAK
• 金额: $ 1.16万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349881
• 关键词: RETINOPETAL; AXONS; MAMMALIAN; RETINAS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long term goal of these experiments is to understand the functions of axons projecting from the brain to the retina, or retinopetal axons. During the last grant period, axons originating from neurons in the hypothalamus and containing histamine were identified in rat and monkey retinas. To determine the functions of these inputs, exogenous histamine was applied to these retinas in vitro while receding from retinal ganglion cells. One of the most striking effects of histamine was the reduction of the light responses in a subset of ganglion cells in monkeys. The proposed experiments will determine whether these are the parasol cells, which contribute to many aspects of vision, particularly the perception of motion. Histamine receptors (HR) were also localized in these retinas by light and electron microscopy. HR1 were localized to large puncta in the inner plexiform layer, a subset of ganglion cells and retinal blood vessels in monkeys. The cells expressing those receptors will be identified in the proposed anatomical experiments. In rat retinas, HR1 receptors were localized to dopaminergic amacrine cells, and the proposed experiments will test the hypothesis that they are inhibitory. This would greatly amplify the effects of histamine because dopamine influences so many types of neurons in the retina. HR1 were also localized to dendrites of rod bipolar cells, and histamine raised intracellular calcium levels in these cells. The proposed physiological experiments will investigate the underlying mechanism and look for other effects of histamine on rod bipolar cells. There is evidence for HR2 in retinas of both species, and these will be localized in the proposed anatomical experiments. HR3 were found at the apex of ON bipolar cell dendrites in cone pedicles and rod spherules of monkeys, at the first synapse in the pathway detecting increments in light intensity. The proposed physiological experiments will study the effects of histamine on macaque bipolar cells. Taken together, these experiments will provide the first comprehensive description of the mechanism by which axons from the brain act on retinal neurons in mammals and provide insight into their roles in primate vision. The experiments dealing with histamine receptors on macaque retinal blood vessels are particularly important because histamine is known to affect retinal blood flow and capillary permeability. Because retinal blood vessels function abnormally in many eye diseases, the results may also be clinically significant.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这些实验的长期目标是了解从大脑投射到视网膜的轴突或视网膜轴突的功能。在最后一次授予期间，在大鼠和猴视网膜中发现了起源于下丘脑神经元并含有组胺的轴突。为了确定这些输入的功能，外源性组胺被施加到这些视网膜在体外，而从视网膜神经节细胞后退。组胺最显着的作用之一是减少猴子神经节细胞子集的光反应。拟议的实验将确定这些是否是阳伞细胞，阳伞细胞有助于视觉的许多方面，特别是对运动的感知。组胺受体（HR）也定位在这些视网膜的光镜和电镜。HR 1定位于大斑点内丛状层，一个子集的神经节细胞和视网膜血管的猴子。表达这些受体的细胞将在拟议的解剖学实验中鉴定。在大鼠视网膜中，HR 1受体定位于多巴胺能无长突细胞，并且所提出的实验将检验它们具有抑制性的假设。这将极大地放大组胺的作用，因为多巴胺影响视网膜中的许多类型的神经元。HR 1也定位于视杆双极细胞的树突，组胺在这些细胞中的细胞内钙水平升高。拟进行的生理学实验将探讨组胺对视杆双极细胞的潜在机制，并寻找组胺对视杆双极细胞的其他影响。在这两个物种的视网膜中有HR 2的证据，这些将在拟议的解剖实验中定位。HR 3被发现在猴子的锥蒂和杆小球的ON双极细胞树突的顶点，在检测光强度增量的通路中的第一个突触。拟进行的生理实验将研究组胺对猕猴双极细胞的影响。总之，这些实验将提供第一个全面的描述机制，从大脑轴突作用于视网膜神经元在哺乳动物和提供洞察他们的作用在灵长类动物的视觉。研究猕猴视网膜血管中组胺受体的实验尤为重要，因为已知组胺会影响视网膜血流和毛细血管通透性。由于视网膜血管在许多眼科疾病中功能异常，因此结果也可能具有临床意义。