THE STRUCTURE OF MITOCHONDRIA IN ROD AND CONE PHOTORECEPTORS

杆状和锥状光感受器中线粒体的结构

• 批准号: 8361904
• 负责人: DONALD A FOX
• 金额: $ 3.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361904
• 关键词: Affect; Aging; Apoptosis; Apoptotic; Cognitive; Darkness; Disease; Electroretinography; Funding; Goals; Grant; Image Analysis; Inherited; Lead; Light; Long-Term Effects; Mitochondria; Mus; National Center for Research Resources; Neurons; Photoreceptors; Presynaptic Terminals; Principal Investigator; Proteins; Rattus; Research; Research Infrastructure; Resources; Retinal; Retinal Cone; Retinal Degeneration; Retinal Photoreceptors; Site; Source; Structure; Transgenic Mice; United States National Institutes of Health; Vertebrate Photoreceptors; Visual; blood Pb concentration; cost; lead exposure; motor deficit; neurotransmitter release; overexpression; postnatal; response; retinal rods; ribbon synapse; toxicant; visual motor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overarching goal of our studies is to develop a comprehensive structural and functional understanding of rod spherule and cone pedicle ribbon synaptic terminals. Vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Photoreceptor apoptosis and visual deficits occur with inherited and toxicant-induced retinal degenerations, diseases, and aging. One such toxicant is lead. Blood lead concentrations equal to or less than the accepted 'safe level' of 10 microgram/dL result in retinal cognitive and visual-motor deficits. Postnatal only lead exposure produces rod-selective apoptosis and a subnormal scotopic electroretinogram (ERG) in mice and rats. Mitochondria in rod inner segments are primary sites of action. The cone inner segment mitochondria are not affected by postnatal lead exposure. However, the mitochondria in the presynaptic terminals of retinal photoreceptors--rod spherules and cone pedicles--have not yet been examined after lead exposure. To determine whether Bcl-xL overexpression, an anti-apoptotic protein, mitigates the long-term effects of postnatal lead exposure on pedicle and spherule mitochondria, we used transgenic mice overexpressing Bcl-xL in photoreceptors.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们研究的首要目标是对杆状小球和锥蒂带状突触末端有一个全面的结构和功能理解。脊椎动物的光感受器是非尖峰神经元，可在黑暗中维持带状突触的持续去极化和神经递质释放，并产生光依赖性分级超极化反应。光感受器凋亡和视力缺陷与遗传性和毒物诱导的视网膜变性、疾病和衰老有关。 其中一种有毒物质是铅。血铅浓度等于或低于公认的“安全水平”10 微克/分升会导致视网膜认知和视觉运动缺陷。 出生后仅接触铅会导致小鼠和大鼠视杆细胞选择性凋亡和暗视视网膜电图 (ERG) 异常。 杆内节中的线粒体是主要作用位点。 锥体内节线粒体不受产后铅暴露的影响。然而，在铅暴露后，视网膜感光细胞突触前末端的线粒体——杆球和锥蒂——尚未被检查。 为了确定 Bcl-xL（一种抗凋亡蛋白）过度表达是否可以减轻出生后铅暴露对椎弓根和小球线粒体的长期影响，我们使用了光感受器中过度表达 Bcl-xL 的转基因小鼠。