THE STRUCTURE OF MITOCHONDRIA IN ROD AND CONE PHOTORECEPTORS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们的研究的首要目标是发展一个全面的结构和功能的理解杆小球和锥椎弓根带状突触终端。脊椎动物光感受器是非尖峰神经元，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。光感受器凋亡和视觉缺陷与遗传性和毒性诱导的视网膜变性、疾病和衰老一起发生。 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。 出生后仅铅暴露可导致小鼠和大鼠视杆细胞选择性凋亡和低于正常的暗视视网膜电图（ERG）。 视杆内节的线粒体是主要的作用部位。 生后铅暴露不影响视锥细胞内节线粒体的功能。然而，视网膜光感受器突触前末梢的线粒体--视杆小球和视锥蒂--在铅暴露后还没有被检测到。 为了确定是否Bcl-xL过度表达，一种抗凋亡蛋白，减轻出生后铅暴露对蒂和小球线粒体的长期影响，我们使用过表达Bcl-xL的转基因小鼠的光感受器。

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.