PROGRESSIVE ROD-CONE DEGENERATION--SYNTHESIS & RENEWAL

进行性视杆细胞退行性变(Prcd)犬的突变体有一个 作为模型的进行性视网膜退行性疾病 治疗人类的视网膜色素变性。这种疾病在地形学上是 定义并以减少的杆状外段(ROS)为特征 续约率。本申请中提出的研究检查了 视网膜蛋白质合成和/或运输之间的联系， 更新率、疾病和退化。与合作者合作 也将与局部视网膜脂肪和蛋白质合成相关 作为考察不同ROS磷脂的组成 上课。这些研究将检验这样一种假设，即扰动 在合成、运输或更新方面的萎缩损害了视觉 细胞，并导致疾病和退化。蛋白质和脂肪 研究将利用体内和体外两种方法。vbl.使用 各种放射性标记的单标记或双标记组合 前体，将有可能检查合成、运输 或新合成的蛋白质或脂类的周转。这些研究 是基于我们维持视网膜结构完整的能力 在器官培养条件下代谢活跃。通过使用 一种保留病种、象限和面积的抽样方法 关系、生化、形态和/或放射自显影 研究将确定疾病和疾病之间的因果关系 观察到的异常。 还建议进行研究，以检查视网膜的变化 存在于prcd基因座的退化表型。中国人民民主共和国- 将使用慢速突变体来建立时间关联 更新率异常与疾病之间的关系。既然是这样 突变人的疾病进展缓慢，病情较轻，建议 实验将确定这是否源于续约率 在较晚的年龄和/或程度较轻时表现出来的缺陷。 另一方面，prcd突变体将被用来检查 局部因素调节疾病，可用于实验 操纵疾病的发展。根据我们最近的发现， 维生素E的组织分布与该病平行 PRCD视网膜的地形图，营养实验将检查 维生素E(边际、适量、过量)水平对健康的影响 疾病的严重程度和进展。这些研究将确定 组织维生素E水平与疾病和 并确定该病的表型是否可以 营养上调节的(加速的、迟缓的)。

The progressive rod-cone degeneration (prcd) dog mutant has a progressive retinal degenerative disorder that serves as a model for retinitis pigmentosa in man. The disease is topographically defined and is characterized by a decreased rod outer segment (ROS) renewal rate. The studies proposed in this application examine the association between retinal protein synthesis and/or transport, renewal rate, disease and degeneration. Work with collaborators will correlate regional retinal lipid and protein synthesis as well as examining the composition of the different ROS phospholipid classes. The studies will test the hypothesis that perturbations wither in synthesis, transport or renewal compromise the visual cell and result in disease and degeneration. The protein and lipid studies will utilize both in vivo and in vitro approaches. Using single or double label combinations of various radioactively tagged precursors, it will be possible to examine the synthesis, transport or turnover of newly synthesized proteins or lipids. These studies are based on our ability to maintain the retina structurally intact and metabolically active under organ culture conditions. By using a sampling method that preserves disease, quadrant and area relationships, the biochemical, morphologic and/or autoradiographic studies will establish the causal relationship between disease and the observed abnormalities. Studies are also proposed to examine the variation in retinal degeneration phenotype that exists at the prcd locus. The prcd- slow mutant will be used to establish the temporal association between the renewal rate abnormality and disease. Since this mutant has a milder and slowly progressive disease, the proposed experiments will determine if this results from a renewal rate defect that is expressed at a later age and/ or to a lesser extent. On the other hand, the prcd mutant will be used to examine whether local factors modulate disease an can be used to experimentally manipulate disease progression. Based on our recent findings that the tissue distribution of vitamin E parallels the disease topography in the prcd retina, nutritional experiments will examine the effect of vitamin E (marginal, adequate, excess) levels on disease severity and progression. These studies will determine the association between tissue vitamin E levels, disease and degeneration and establish if the disease phenotype can be modulated (accelerated, retarded) nutritionally.