Novel model systems for the study of cone disorders and other heritable retinal diseases

用于研究视锥细胞疾病和其他遗传性视网膜疾病的新型模型系统

基本信息

  • 批准号:
    10483221
  • 负责人:
  • 金额:
    $ 129.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-30 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Retinal degeneration diseases are a common cause of untreatable blindness worldwide, affecting the lives of millions. The only FDA-approved treatment for these disorders is gene therapy for specific RPE65 mutations that cause Leber’s congenital amaurosis and retinitis pigmentosa. One major limitation to the development of effective therapies is the use of model systems that poorly replicate the human condition. Particularly for cone disorders, studies that use model systems with a rod-dominant retina and no true macula have substantive limitations. We propose to develop a series of novel and spontaneous animal models of human inherited retinal diseases. In preliminary analyses, we have identified a new spontaneous model directly relevant to human retinal disease. Genetic testing identified four individuals homozygous for a naturally occurring damaging mutation in the PDE6C gene, which has previously been associated with cone dystrophy in humans. Scotopic and photopic full-field electroretinograms performed on animals homozygous for the PDE6C mutation demonstrated a relatively normal rod response but no cone response whatsoever. A subtle but characteristic retinopathy was identified using fundus photography, blue autofluorescence, and fluorescein angiography with concurrent foveal thinning using spectral-domain optical coherence tomography. Our genetic survey also identified individuals with mutations in 7 other human retinal disease genes that are predicted to severely damage gene or protein function, pointing to possible additional new models. To develop the new model of PDE6C cone dystrophy, and make this and other new models available to the vision research community, we propose four Specific Aims: 1) to identify and genetically characterize new animal models of human retinal disease via DNA sequencing, 2) to perform complete ophthalmic phenotyping of the new models of retinal disease, 3) to breed a colony of animals with PDE6C cone dystrophy and 4) to compare cell-based and gene replacement therapies in these subjects with PDE6C cone dystrophy mutations. Successful completion of this work will produce a well-characterized new animal model of inherited cone dystrophy with significantly greater similarity to human disease than existing models, thus providing substantially better translation to subsequent human trials. In addition, affected animals will be made available to the wider vision research community, and other new models with similar potential will be identified.
项目总结/文摘

项目成果

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RUI CHEN其他文献

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{{ truncateString('RUI CHEN', 18)}}的其他基金

Comprehensive Somatic Variant Characterization at the HGSC
HGSC 的综合体细胞变异表征
  • 批准号:
    10662645
  • 财政年份:
    2023
  • 资助金额:
    $ 129.42万
  • 项目类别:
Single Cell Spatial Transcriptomics Shared Instrument at the BCM Core Facility
BCM 核心设施的单细胞空间转录组学共享仪器
  • 批准号:
    10414324
  • 财政年份:
    2022
  • 资助金额:
    $ 129.42万
  • 项目类别:
Deep-Learning-Derived Endophenotypes from Retina Images
来自视网膜图像的深度学习衍生的内表型
  • 批准号:
    10706984
  • 财政年份:
    2022
  • 资助金额:
    $ 129.42万
  • 项目类别:
Effects of cornea epithelial barrier disruption on the cornea trigeminal neural circuit
角膜上皮屏障破坏对角膜三叉神经回路的影响
  • 批准号:
    10586519
  • 财政年份:
    2022
  • 资助金额:
    $ 129.42万
  • 项目类别:
Deep-Learning-Derived Endophenotypes from Retina Images
来自视网膜图像的深度学习衍生的内表型
  • 批准号:
    10392211
  • 财政年份:
    2022
  • 资助金额:
    $ 129.42万
  • 项目类别:
Effects of cornea epithelial barrier disruption on the cornea trigeminal neural circuit
角膜上皮屏障破坏对角膜三叉神经回路的影响
  • 批准号:
    10708182
  • 财政年份:
    2022
  • 资助金额:
    $ 129.42万
  • 项目类别:
Modeling Frontotemporal Dementia in Rhesus Macaques
恒河猴额颞叶痴呆模型
  • 批准号:
    10626978
  • 财政年份:
    2019
  • 资助金额:
    $ 129.42万
  • 项目类别:
Modeling Frontotemporal Dementia in Rhesus Macaques
恒河猴额颞叶痴呆模型
  • 批准号:
    10599018
  • 财政年份:
    2019
  • 资助金额:
    $ 129.42万
  • 项目类别:
Modeling Frontotemporal Dementia in Rhesus Macaques
恒河猴额颞叶痴呆模型
  • 批准号:
    9894456
  • 财政年份:
    2019
  • 资助金额:
    $ 129.42万
  • 项目类别:
Modeling Frontotemporal Dementia in Rhesus Macaques
恒河猴额颞叶痴呆模型
  • 批准号:
    10023200
  • 财政年份:
    2019
  • 资助金额:
    $ 129.42万
  • 项目类别:

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