Disk Renewal in Retinal Visual Cells

描述（由申请人提供）：我们的目标是了解 光暗周期和光感受器昼夜节律钟在控制外显 视网膜的节律生理学。该应用程序利用了最近 发现周期基因对昼夜节律和光至关重要 生物钟的反应。我们将研究光的作用， 多巴胺反应期基因（xPer 2）在视网膜节律生理学中的作用。的 应用程序的基础模型是，xPer 2在以下方面发挥着重要作用： 协调光暗周期与内源性时钟的影响。我们将 研究（1）光和多巴胺诱导xPer 2上调与 其他时钟基因的表达，（2）过度表达的后果， 使用爪蟾转基因的光感受器-RPE复合物中的xPer 2，和（3） 使用核连续测定的xPer 2基因的转录调控。一 中心假设是xPer 2基因的蛋白产物与 视网膜生物钟的其他循环成分来调节相位 重置光和多巴胺的作用破坏这些相互作用， 恒定的光被提出来解释昼夜节律的破坏， 已知的感光膜更新的改变。

DESCRIPTION (provided by applicant): Our goal is to understand the role of light-dark cycles and a photoreceptor circadian clock in the control of overt rhythmic physiology in the retina. This application capitalizes on the recent discovery that Period genes are critical to circadian rhythmicity and to light responses of the circadian clock. We will study the role of a light- and dopamine-responsive period gene (xPer2) in rhythmic retinal physiology. The model underlying the application is that xPer2 plays an important role in coordinating the effects of light-dark cycles with an endogenous clock. We will study (1) light- and dopamine-induced up-regulation of xPer2 in relationship to expression of other clock genes, (2) the consequences of over-expression of xPer2 in the photoreceptor-RPE complex using Xenopus transgenesis, and (3) transcriptional regulation of the xPer2 gene using nuclear run-on assays. A central hypothesis is that the protein product of the xPer2 gene interacts with other cycling components of the retinal circadian clock to mediate the phase resetting effects of light and dopamine. Disruption of these interactions in constant light is proposed to account for disruption of circadian rhythms and for known alterations in photoreceptor membrane turnover.