SURVIVAL & MATURATION OF NORMAL & MUTANT PHOTORECEPTORS

光感受器死亡导致视网膜变性失明，例如 视网膜色素变性和老年性黄斑变性。虽然 遗传机制触发了这些疾病的几种形式，细胞-细胞 相互作用和微环境因素也可能参与其中。 在他们的发病机制中。寻找营养物质支持 因此，光感受器细胞的存活和分化功能 对于制定其预防和/或战略很重要 治疗。胚胎细胞移植--一种积极探索的方法 在许多实验室中，作为治疗视网膜退化的可能方法-- 也可能受益于有关光感受器存活的新信息--以及 促进分化的因素。 维生素A家族的维甲酸多年来一直被认为是 对于感光器的健康和生存是必要的，但它们的机制 人们对行动仍然知之甚少。他们的调查有新的途径 近几年来，随着信息量的爆炸性增长， 关于维甲酸及其受体。作为我们长期利益的一部分 在对光感受器细胞的营养因子的研究中，我们最近 维甲酸等维甲酸对大鼠血管紧张素转换酶的调节作用 体外分离小鼠光感受器细胞。因此，这些文化系统 作为详细分析这些问题的合适的实验系统 问题。这里提出的研究将涉及胚胎和新生儿。 小鼠视网膜的原位培养和组织块培养以及纯化 视网膜神经元和光感受器的培养。原位杂交，即 聚合酶链式反应、免疫细胞化学和放射自显影 方法将以多学科的方式使用来研究 视黄酸受体及其受体的表达和分布 发育调节，以及视网膜神经元和 视黄酸和其他类维甲酸的光感受器。这是意料之中的 这些研究将产生新的信息，关于 维甲酸在光感受器分化和存活中的作用 为预防和潜在的治疗疾病制定战略 导致失明的视网膜变性。

Photoreceptor death causes blindness in retinal degenerations such as retinitis pigmentosa and age-related macular degeneration. Although genetic mechanisms trigger several forms of these diseases, cell-cell interactions and microenvironmental factors are also likely to be involved in their pathogenesis. The search for trophic agents supporting the survival and differentiated function of photoreceptor cells is therefore important for the development of strategies for their prevention and/or treatment. Embryonic cell transplantation -- an approach actively explored in many laboratories as a possible treatment for retinal degenerations -- could also benefit from new information on photoreceptor survival- and differentiation-promoting factors. Retinoids of the vitamin A family have been known for many years to be necessary for photoreceptor health and survival, but their mechanisms of action remain poorly understood. New avenues for their investigation have been opened in recent years by the almost explosive growth in information about retinoic acid and its receptors. As part of our long term interest in the study of trophic factors for photoreceptor cells, we have recently observed regulatory effects of retinoic acid and other retinoids upon isolated mouse photoreceptor cells in vitro. These culture systems thus appear as suitable experimental systems for detailed analysis of these issues. The studies proposed here will involve embryonic and neonatal mouse retinas in situ and in explant cultures, as well as purified cultures of retinal neurons and photoreceptors. In situ hybridization, the polymerase chain reaction, and immunocytochemical and autoradiographical methods will be used in a multidisciplinary approach to investigate the expression and distribution of retinoic acid receptors, their developmental regulation, and the responses of retinal neurons and photoreceptors to retinoic acid and other retinoids. It is anticipated that these studies will generate new information regarding the role of retinoids in photoreceptor differentiation and survival, thus contributing to the design of strategies for the prevention and potential treatment of blinding retinal degenerations.