Genetic Analysis of Retinal Degeneration

视网膜变性是由大量光感受器表达基因的突变引发的。给定 由于这些基因的生物化学作用的多样性，每个突变体必须具有不同的主要影响， 感光细胞生物学值得注意的是，视网膜变性是由多种遗传损伤引起的 通过相似的形态学标志，提示共享细胞死亡事件的可能性。期间 在前一个授予周期中，成功地采用了一种无偏见的方法来鉴定作用于 这些视网膜退化过程。在用于视觉研究的实验动物中，这种类型的 这种方法只在果蝇中可行。值得注意的是，该方法涉及非半胱天冬酶依赖性的 细胞死亡途径作为视网膜疾病进展的关键组成部分。这三个目标 该提案侧重于分析这些途径的已确定分子组成部分。他们在 退化过程将通过遗传学、细胞生物学和分子方法相结合来研究。 这项工作有望为控制视网膜病变的细胞机制提供新的信息。 退化因此，该提案涉及国家计划的主要目标之一， 2004年，国家眼科研究所。这个五年计划包括，在视网膜疾病的类别，以"确定 基因参与遗传和视网膜变性疾病，并决定病理生理 这些突变引发的疾病进展的潜在机制”。

Retinal degeneration is triggered by mutations in a large number of photoreceptor-expressed genes. Given the diversity of biochemical roles of these genes, each mutant must have distinct primary effects on photoreceptor cell biology. It is remarkable that the diversity of genetic insults result in retinal degeneration via similar morphological landmarks, suggesting the possibility of shared cell death events. During the previous granting cycle, an unbiased approach was successfully employed to identify genes that act in these retinal degeneration processes. Among experimental animals used in vision research, this type of approach is feasible only in Drosophila. Significantly, the approach has implicated non-caspase dependent pathways of cell death as the critical component in the progression of retinal disease. The three aims of this proposal focus on the analysis of identified molecular components of these pathways. Their role in the degeneration process will be studied by a combination of genetic, cell biological and molecular approaches. The effort is expected to provide new information on the cellular mechanisms controlling retinal degeneration. Thus, the proposal addresses one of the major goals of the National Plan released by the National Eye Institute in 2004. This five year plan includes, in the category of retinal disease, to "identify the genes involved in both inherited and retinal degenerative diseases and determine the pathophysiological mechanisms underlying the disease progression triggered by these mutations".