MODELS OF HEREDITARY RETINAL DEGENERATION

该应用程序建议继续执行已被 由首席调查员连续管理了16年以上。这个 项目目的由两部分组成。一是发挥中心研究作用 用于生产和分配的资源，用于其他独立研究 4个遗传性视网膜犬种突变模型的研究人员 影响人类的退化。对这些犬类突变体的需求 研究被解决了，以及在一个 集中饲养和分配设施。第二个目标是 继续进行已经建立的合作研究，以克隆 这些疾病，研究这些疾病的细胞和分子生物学 疾病，并开发治疗干预的方法。每一个这样的 协作学习是同行评审，作为 合作调查员的研究协议。 四个品系的狗，每个品系传递一种不同的基因 特征性遗传性视网膜变性(视杆-视锥细胞发育不良1型 RCD1，进行性视杆细胞视锥细胞变性，早期视网膜变性 ERD、视锥退行性变CD)，以及适当的未受影响的对照 狗，将被饲养和维护。这些狗的后代将是 直接或通过收集分发给研究人员， 加工和分发所需的组织。这些资源的利用 将通过征求调查人员的请求来促进突变体的发展。 将向开发和开发方面的调查人员提供援助 执行特定协议，以最大限度地利用这些资源 变种人。 具体的协作研究包括以下计划：识别、克隆和 确定cd、erd和prcd基因突变的特征；确定和 比较程序性细胞死亡基因在CD、ERD、PrCD和RCD1中的作用； 确定二十二碳六酸转运异常的原因 PRCD中的新陈代谢并确定与此相关的候选基因 缺陷；进一步开发遗传性视网膜的治疗方法 包括载体介导的犬基因转移在内的退行性疾病 光感受器、光感受器和视网膜色素上皮细胞 犬视网膜移植；视觉假体的应用 硅胶视网膜植入物。

The application proposes continuation of a resource project that has been continuously managed by the principal investigators for over 16 years. The project purpose has 2 parts. The first is to serve as a central research resource for production and distribution, to other independent research investigators, of 4 canine mutant models of the hereditary retinal degenerations affecting humans. The need for these canine mutants in research is addressed, as is the importance of maintaining them in a centralized breeding and distribution facility. The second objective is to continue collaborative studies already established to clone the genes for these diseases, investigate the cellular and molecular biology of these diseases, and develop methods for therapeutic intervention. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Four strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcd1, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd), together with appropriate nonaffected control dogs, will be bred and maintained. The progeny of these dogs will be distributed to research investigators, either directly or by collection, processing and distribution of requested tissues. Utilization of these mutants will be promoted by solicitation of requests from investigators. Assistance will be offered to investigators in development and implementation of specific protocols for optimal utilization of these mutants. Specific collaborative research includes programs to: identify, clone, and characterize the gene mutations for cd, erd and prcd; determine and compare the role of programmed cell death genes in cd,erd, prcd, and rcd1; define the cause of abnormalities in docosahexanoic acid transport & metabolism in prcd and identify candidate genes responsible for these deficiencies; further develop therapies for hereditary retinal degenerations including vector mediated gene transfer into canine photoreceptors; photoreceptor and retinal pigment epithelial cell transplantation into canine retina; and application of a visual-prosthetic silicon retinal implant.