PHOTORECEPTORS--EFFECTS OF DIFFERENTIATION FACTORS

虽然许多研究利用两栖动物、鸟类和哺乳动物组织 提示色素上皮(PE)是外膜的必需成分。 膜段生产的正常数量和结构，准确 发生这种情况的机制(S)尚不清楚。PE可以服务于一个或多个 对底层光感受器细胞的更多功能支持，即 适当的微环境，通过结构模板 光感受器基质或某些营养因子的来源(S) 调控基因表达。在这项建议中，私募股权基金在 感光细胞分化和外节段膜组织 使用体外模型进行系统研究，其中视网膜将 在未分化的状态下被移出培养。视网膜成熟， 在PE的存在和不存在的情况下精心设计外部部分， 然而，在没有膜的情况下，膜是杂乱无章的。因为 在没有PE的情况下，光感受器确实会产生外节膜 可以利用该系统来确定什么因素(S)能够改变 膜的组织和蛋白质的合成 在那里。视蛋白和视黄醇受体间结合蛋白(IRBP)基因 表达和蛋白质合成以及外段组织 将在没有PE的情况下成熟的视网膜进行比较和对比 在存在各种潜在差异化的情况下，与没有PE的对比 因素包括乳糖、生长因子、维甲酸和IRBP。体育运动 毫无疑问，在……的发展过程中， 光感受器。在测试时，任何一个组件都不太可能 仅此一项就可以恢复完整水平的表达和合成 光感受器特异性分化标志物。然而，一个系统化的 评估每一项测试条件的增强能力 高于控制水平的表达和合成提供了一种直接的方法 识别可由PE提供的各种组件 支持感光细胞分化。

While many investigations utilizing amphibian, avian and mammalian tissue have suggested that the pigment epithelium (PE) is necessary for outer segment membrane production of normal quantity and structure, the exact mechanism(s) by which this occurs is not known. The PE may serve one or more functional supports to the underlying photoreceptor cells, i.e.,the appropriate microenvironment, a structural template via the interphotoreceptor matrix or be the source of some trophic factor(s) that regulate gene expression. In this proposal, the role of the PE on photoreceptor differentiation and outer segment membrane organization will be systematically explored using an in vitro model in which retinas will be removed to culture in an undifferentiated state. The retinas mature and elaborate outer segments in both the presence and absence of the PE, however the membranes are disorganized in its absence. Because photoreceptors do produce outer segment membrane in the absence of the PE the system can be exploited to determine what factor(s) are able to alter the organization of the membranes and the synthesis of the proteins therein. Opsin and interphotoreceptor retinoid binding protein (IRBP) gene expression and protein synthesis as well as outer segment organization will be compared and contrasted in retinas allowed to mature without a PE vs. without a PE yet in the presence of various potential differentiation factors including lactose, growth factors, retinoids and IRBP. The PE undoubtedly plays a number of complex roles during the development of photoreceptors. It is unlikely that any one of the components when tested alone would restore a full level of expression and synthesis of the photoreceptor specific differentiation markers. However, a systematic assessment of the ability of each of the test conditions to enhance expression and synthesis above control levels offers a direct approach to identifying the various components that could be provided by the PE which support photoreceptor differentiation.