MODELS OF HEREDITARY RETINAL DEGENERATION

该申请建议继续一个资源项目， 由主要研究者持续管理超过16年。的 项目目的有两个部分。一是作为中央研究 生产和分销资源，其他独立研究 研究人员，4犬突变模型的遗传性视网膜 影响人类的退化需要这些犬类突变体 研究是解决，因为是保持他们在一个 集中饲养和分配设施。第二个目标是 继续已经建立的合作研究，克隆基因， 研究这些疾病的细胞和分子生物学， 疾病，并制定治疗干预的方法。 每个这样 合作研究是同行评审，单独，作为一部分， 合作研究者的研究协议。 四个品种的狗，每一个都传递了不同的基因， 特征性遗传性视网膜变性（视杆-视锥发育不良1型 rcd 1，进行性视杆-视锥变性，早期视网膜变性 erd，视锥细胞变性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， 处理和分发所需组织。利用这些 变种人将通过向调查人员征求请求而得到晋升。 将向调查人员提供发展方面的援助， 执行具体的协议，以最佳利用这些 变种人 具体的合作研究包括：识别，克隆， 表征cd、erd和prcd的基因突变;确定和 比较程序性细胞死亡基因在CD、ERD、PRCD和RCD 1中的作用; 确定二十二碳六烯酸转运异常的原因， 代谢在PRCD和确定候选基因负责这些 进一步开发遗传性视网膜病变的治疗方法 包括载体介导的基因转移到犬中的退化 光感受器和视网膜色素上皮细胞 移植到狗视网膜中;以及视觉假体的应用 硅视网膜植入物

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.