PROGRESSIVE ROD-CONE DEGENERATION: SYNTHESIS & RENEWAL

渐进杆锥退化：合成

• 批准号: 3255821
• 负责人: GUSTAVO David AGUIRRE
• 金额: $ 21.08万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3255821
• 关键词: antioxidants; autoradiography; cone cell; congenital eye disorder; cyclic nucleoside monophosphate; dogs; electron microscopy; electroretinography; gene expression; infant animal; lipid biosynthesis; lipid transport; mutant; nucleic acid metabolism; organ culture; phospholipids; protein biosynthesis; protein transport; radiotracer; retina degeneration; rod cell; tocopherols

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.

渐进性视杆锥变性（PRCD）狗突变体具有 作为模型的进行性视网膜退行性疾病 用于男性色素性视网膜炎。 该病与地形有关 定义并以杆外节 (ROS) 减少为特征 续订率。 本申请中提出的研究考察了 视网膜蛋白质合成和/或运输之间的关联， 更新率、疾病和退化。 与合作者一起工作 也将关联区域视网膜脂质和蛋白质合成 检查不同 ROS 磷脂的组成 类。 这些研究将检验扰动的假设 在合成、运输或更新中枯萎会损害视觉效果 细胞并导致疾病和退化。 蛋白质和脂质 研究将利用体内和体外方法。 使用 各种放射性标记的单或双标记组合 前体，将有可能检查合成、运输 或新合成的蛋白质或脂质的周转。 这些研究 基于我们维持视网膜结构完整的能力 并在器官培养条件下具有代谢活性。 通过使用 保留疾病、象限和面积的采样方法 关系、生化、形态学和/或放射自显影 研究将确定疾病与疾病之间的因果关系 观察到的异常情况。 还建议进行研究以检查视网膜的变化 存在于prcd基因座的变性表型。 pcd- 慢突变体将用于建立时间关联 更新率异常与疾病之间。 自从这 突变体具有较温和且进展缓慢的疾病，建议 实验将确定这是否是由于更新率造成的 在较晚的年龄和/或程度较小的情况下表现出的缺陷。 另一方面，prcd突变体将用于检查是否 局部因素调节疾病，可用于实验 操纵疾病进展。 根据我们最近的发现 维生素 E 的组织分布与疾病相关 营养实验将检查 PRCD 视网膜的地形 维生素 E（边际、充足、过量）水平对健康的影响 疾病的严重程度和进展。 这些研究将决定 组织维生素E水平与疾病之间的关系 变性并确定疾病表型是否可以 营养调节（加速、延迟）。