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 在感觉的发育和维持中起着重要的作用 功能。任何一种成分的丢失都可能导致其他细胞的萎缩， 导致感官缺陷。光感受器丧失是导致 几种视网膜退行性疾病的视力损害，如 视网膜色素变性和黄斑变性。感觉障碍 曾被认为是由神经组织的退化引起的 不可逆转。新的可能性被提出为理解 光感受器退化的生化和分子机制 动物模型的增加，如RD(视网膜变性)小鼠。 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 刺激了神经感觉移植的研究。最近，这个实验室 已经提出证据表明正常的感光器从 健康的小鼠可以挽救RD小鼠的视锥感光细胞。这是 在动物模型中进行神经感觉救援的第一个实例 人类感觉营养不良。 这一建议是基于一个假设，即正常的杆状感光器 对视锥感光细胞和支持细胞有营养作用，如 视网膜色素上皮(RPE)。这项研究的长期目标是 为了加深对分子变化的理解， RD小鼠视锥细胞和RPE的继发性变性及其发育 防止或尽量减少这种损失的方法。为实现这些目标，(I) 正常的小鼠光感受器将被移植到RD小鼠体内 然后进行统计和形态计量分析，以衡量 移植细胞对宿主细胞存活的影响，(2)器官培养 系统将与正常和营养不良的视网膜组织一起开发 模拟体内模型和(3)器官培养体系 利用已知的营养因子来调节感觉细胞的生长 更好地了解维护过程中涉及的分子机制 以及感觉和支持细胞的存活。 拟议的重返大气层培训方案建立在以前培训的基础上， 重建视网膜研究和技术的现有知识 在光学和电子显微镜方面的专业知识。新的培训将强调 了解神经营养因子和细胞及器官培养技术。 这些元素将被用于建立一个专注于营养的研究计划 视觉系统中神经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.