Modulators of Retinal Injury

视网膜损伤的调节剂

• 批准号: 7908773
• 负责人: ELDON E GEISERT
• 金额: $ 32.52万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908773
• 关键词: Accounting; Affect; Age-Months; Animal Model; Axon; Bioinformatics; Biological Models; Cell Death; Cell Survival; Collaborations; Data; Data Set; Disease; Experimental Models; Eye; Foundations; Gene Expression Profile; Genes; Genetic; Genomics; Glaucoma; Goals; Injury; Molecular Profiling; Mouse Strains; Mus; Nerve Crush; Nerve Degeneration; Optic Nerve; Pattern; Positioning Attribute; Predisposition; Process; Property; Quantitative Trait Loci; Recombinant Inbred Strain; Recombinants; Resistance; Retina; Retinal; Retinal Ganglion Cells; Running; Series; Single Nucleotide Polymorphism Map; Structure; Testing; Time; Transcript; Work; analytical tool; density; ganglion cell; injured; interest; mouse model; response; retinal axon

DESCRIPTION (provided by applicant): Our group is interested in the response of the retina to injury. Recently we expanded our approach looking at a large segment of the transcriptome using microarrays and bioinformatics. During this process a unique compelling opportunity focused our collective interest on a project looking at retinal axon damage (optic nerve crush) in the mouse as a model system. In collaboration with the Rob Williams' group we are using the BXD recombinant inbred (Rl) strains to define genetic networks in the eye and retina. These interactions have put us in a unique position to study the early signature of retinal injury and genomic loci that may underlie susceptibility or resistance to optic nerve damage. The long-term goal of this project is to define genetic networks controlling susceptibility and resistance of the retina to optic nerve damage and to characterize the early molecular signatures associated with these changes. Our working hypothesis is that the differential vulnerability of the retina is modulated by network of polymorphic genes that contribute to susceptibility or resistance to neurodegeneration and ganglion cell death. We will use a unique set of isogenic strains of mice (the BXD Rl strains) to investigate an experimental model of optic nerve damage. This large set of strains is uniquely suited to study the genetics of optic nerve damage because one of the parental strains is susceptible to injury (DBA/2J strain) whereas the other strain is resistant (C57BL/6 strain). This work exploits the unique properties of this particular strain panel in three specific aims. Aim 1 will define the normal patterns of transcriptional activity in the retinas of recombinant inbred strains. The transcriptional networks identified in these uninjured mice will serve as a background to define the changes occurring after optic nerve damage. Aim 2 will test the hypothesis that there are a series of transcriptome signatures in the retina of the BXD Rl strains that are predictive of susceptibility or resistance of ganglion cell death after axon injury. These data will define the common and unique genetic networks that are activated following injury to the optic nerve axons and will define the early changes associated with optic nerve damage. Finally we will be able to identify the genetic networks controlling susceptibility and resistance to ganglion cell death.

描述（由申请人提供）：我们的小组对视网膜对伤害的反应感兴趣。最近，我们使用微阵列和生物信息学扩展了大量转录组的方法。在此过程中，一个独特的引人注目的机会将我们的集体兴趣集中在鼠标中的视网膜轴突损伤（视神经挤压）上作为模型系统。在与Rob Williams组合作的情况下，我们使用BXD重组近交（RL）菌株来定义眼睛和视网膜中的遗传网络。这些相互作用使我们处于一个独特的位置，可以研究视网膜损伤和基因组基因瘤的早期特征，这可能是对视神经损伤的敏感性或抵抗力的基础。该项目的长期目标是定义控制视网膜对视神经损害的敏感性和抗性的遗传网络，并表征与这些变化相关的早期分子特征。我们的工作假设是，视网膜的差异脆弱性是由多态性基因网络调节的，这些基因有助于神经变性或神经节细胞死亡的敏感性或抗性。我们将使用一组独特的小鼠（BXD RL菌株）的异源性菌株研究视神经损伤的实验模型。这组大型菌株非常适合研究视神经损伤的遗传学，因为其中一种亲本菌株易于受伤（DBA/2J菌株），而另一种菌株则具有抗性（C57BL/6菌株）。这项工作以三个特定目标利用了该特定应变面板的独特性能。 AIM 1将定义重组近交菌株视网膜中转录活性的正常模式。这些未受伤的小鼠中鉴定出的转录网络将作为定义视神经损伤后发生的变化的背景。 AIM 2将检验以下假设：BXD RL菌株的视网膜中存在一系列转录组特征，这些特征可预测轴突损伤后神经节细胞死亡的敏感性或抗性。这些数据将定义在视神经轴突受伤后激活的常见和独特的遗传网络，并将定义与视神经损伤相关的早期变化。最后，我们将能够确定控制易感性和对神经节细胞死亡的耐药性的遗传网络。