MECHANISMS OF PHOTORECEPTOR OUTER SEGMENT DEVELOPMENT

本研究的长期目标是调查可能的作用 视网膜微环境的变化， 光感受器的一个专门过程，称为外节。 关于可能在这一过程中发挥作用的因素，人们知之甚少。 诱导过程，或这些推定信号可能 来了此外，外节是一个不稳定的结构， 在许多疾病的动物模型中显示病理学的第一个元素 流程.因此，研究发展的必要因素， 外节也将是重要的，在了解什么元素， 是必要的诱导，形成，和维护外部 段，以及可能的治疗策略的设计，为人类 视网膜变性疾病 以下具体目标将有助于 实现这一目标：1）表征发展中IPM中的蛋白质 这可能在使用组织化学的外节诱导中起作用， 半定量方法; 2）光感受器细胞容量的研究 使用低密度培养物形成作为年龄函数的外节 从分期胚胎，和3）研究细胞-细胞接触的作用， 光感受器中的扩散因子和细胞外基质分子 使用高密度视网膜和高密度视网膜的组合的外节诱导 培养物、聚合物培养物和条件培养物的生长 培养基和/或细胞外基质调节的板。

The long term objective of this study is to investigate the possible role of changes in the retinal microenvironment that induce the formation of a specialized processes of photoreceptors, known as the outer segment. Little is known regarding the elements that may play a role in the inductive process, or the source from which these putative signal(s) may come. In addition, the outer segment is a labile structure that is the first element to show pathology in animal models of many disease processes. Thus, the study of elements necessary for the development of outer segments will also be important in understanding what elements may be necessary for the induction, formation, and maintenance of outer segments, and the possible design of therapeutic strategies for human degenerative retinal diseases. The following specific aims will help obtain this objective: 1) Characterize proteins in the developing IPM that may play a role in outer segment induction using histochemistry and semi-quantitative methods, 2) Study the capacity of photoreceptor cells to form outer segments as a function of age using low density cultures from staged embryos, and 3) investigate the role of cell-cell contacts, diffusible factors, and extracellular matrix molecules, in photoreceptor outer segment induction using a combination of high and density retinal cultures, aggregate cultures, and growth of cultures in conditioned medium and/or extracellular matrix-conditioned plates.