NEUROTROPHIC FACTORS IN SENSORY CELL ATROPHY AND RESCUE

感觉细胞、神经元和支持细胞之间的营养相互作用 在发展和维持感官方面发挥重要作用 功能任何一种成分的缺失都可能导致其他细胞的萎缩， 导致感觉缺失。光感受器丧失是导致 在几种视网膜变性疾病中的视觉损害， 视网膜色素变性和黄斑变性。感官上的缺陷 曾被认为是神经组织退化的结果 不可逆的新的可能性正在被提出， 光感受器变性的生化和分子机制 在动物模型如RD（视网膜变性）小鼠中增加。 此外，最近的神经移植努力与退行性变有关， 帕金森氏症、亨廷顿氏症和阿尔茨海默氏症等脑部疾病 刺激神经感觉移植的研究。最近，这个实验室 已经提出了证据表明，正常的光感受器移植从 健康小鼠可以拯救RD小鼠中的视锥光感受器。这是 第一次在动物模型中进行神经感觉拯救， 人类感觉营养不良 这一建议是基于这样的假设，即正常的视杆细胞感光器 对视锥光感受器和支持细胞具有营养作用， 视网膜色素上皮（RPE）。这项研究的长期目标是 来了解这些变化背后的分子变化， rd小鼠视锥细胞和RPE的继发性变性， 防止或减少这种损失的方法。为了实现这些目标，（一） 将正常的小鼠光感受器移植到RD小鼠中 然后进行统计学和形态学分析，以测量 移植细胞对宿主细胞的存活，（2）器官培养 将用正常和营养不良视网膜组织开发系统， 模拟体内模型和（3）器官培养系统将 用已知介导感觉细胞生长的营养因子操纵， 更好地理解维持的分子机制 以及感觉和支持细胞的存活。 拟议的重返社会培训方案以以往的培训为基础， 重建视网膜研究和技术的现有知识 光学和电子显微镜的专业知识。新的培训将强调 神经营养因子和细胞及器官培养技术的知识。 这些元素将用于建立一个研究计划，重点是营养 视觉系统中神经细胞和支持细胞之间的相互作用。

Trophic interactions among sensory cells, neurons and supporting cells play an important role in the development and maintenance of sensory function. Loss of any one component may lead to atrophy of other cells, resulting in sensory deficit. Photoreceptor loss is the primary cause of visual impairment in several retinal degenerative diseases such as retinitis pigmentosa and macular degeneration. Sensory impairment resulting from degeneration of neural tissue was once considered irreversible. New possibilities are being raised as understanding of biochemical and molecular mechanisms of photoreceptor degeneration increases in animal models such as the rd (retinal degeneration) mouse. Furthermore, recent neural transplantation efforts related to degenerative brain diseases such as Parkinson's, Huntington's and Alzheimer's have stimulated research on neurosensory transplantation. Recently, this lab has presented evidence that normal photoreceptors transplanted from healthy mice can rescue cone photoreceptors in the rd mouse. This is the first instance of neurosensory rescue in an animal model relevant for a human sensory dystrophy. This proposal is based on the hypothesis that normal rod photoreceptors have a trophic effect on cone photoreceptors and supporting cells such as retinal pigment epithelium (RPE). The long term goal of this research is to develop an understanding of the molecular changes that underlie the secondary degeneration of cones and RPE in the rd mouse and to develop methods to prevent or minimize this loss. To achieve these goals, (I) normal mouse photoreceptors will be transplanted into the rd mouse followed by statistical and morphometric analysis to measure the effect of the transplanted cells on the survival of host cells, (2) an organ culture system will be developed with normal and dystrophic retinal tissue to simulate the in vivo model and (3) the organ culture system will be manipulated with trophic factors known to mediate sensory cell growth to better understand what molecular mechanisms are involved in maintenance and survival of sensory and supporting cells. The proposed re-entry training program builds on previous training by reestablishing both current knowledge of retinal research and technical expertise in light and electron microscopy. New training will emphasize knowledge of neurotrophic factors and cell and organ culture techniques. These elements will be use to build a research program focusing on trophic interactions between neural and support cells in the visual system.