Cytokine Regulation of Photoreceptor Gene Expression

光感受器基因表达的细胞因子调节

• 批准号: 7175362
• 负责人: John D Ash
• 金额: $ 28.27万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-02 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7175362
• 关键词: Address; Adult; Adverse effects; Bipolar Neuron; Blindness; Cell Death; Cell Differentiation Inhibition; Cell Survival; Cessation of life; Ciliary Neurotrophic Factor; Clinical Trials; Data; Development; Event; Eye; Gene Expression; Genes; Inherited; Knockout Mice; Ligands; Light; Measures; Modeling; Muller' s cell; Mus; Neurologic; Opsin; Pathway interactions; Patients; Photoreceptors; Problem Solving; Regulation; Research Personnel; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinitis Pigmentosa; Role; Signal Transduction; Stem cell transplant; Technology; Testing; Therapeutic; Tissues; Transgenic Mice; Transplantation; Vertebrate Photoreceptors; cell type; cytokine; interest; leukemia inhibitory factor; loss of function; neuroblast; neuroprotection; prevent; programs; receptor; recombinase; relating to nervous system; research study; response; retinal neuron; retinal rods; synaptogenesis; theories

DESCRIPTION (provided by applicant): Neurological cytokines have shown tremendous therapeutic potential for preventing or delaying blindness. Several of these cytokines stimulate the receptor gp130. Stimulation with either leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) has three profound effects on retinal cells: inhibition of differentiation; neuroprotection from retinal degeneration; and reduced light response of photoreceptors. Despite the interest in these effects, little is known about the role of gp130 in normal retinal development or its role in preventing photoreceptor death. In this study we will use tissue specific inactivation of gp130 to address three important questions. 1. What is the role gp130 in normal differentiation of the retina? 2. Is gp130 expression in photoreceptors or Muller cells responsible for neuroprotection and function loss? 3. Is the PI3K/Akt pathway responsible for gp130 induced neuroprotection?

描述（由申请人提供）：神经细胞因子已显示出预防或延缓失明的巨大治疗潜力。其中一些细胞因子刺激受体 gp130。白血病抑制因子 (LIF) 或睫状神经营养因子 (CNTF) 的刺激对视网膜细胞产生三种深远的影响：抑制分化；预防视网膜变性的神经保护；并降低光感受器的光响应。尽管人们对这些作用很感兴趣，但人们对 gp130 在正常视网膜发育中的作用或其在防止光感受器死亡中的作用知之甚少。在本研究中，我们将利用 gp130 的组织特异性失活来解决三个重要问题。 1. gp130在视网膜正常分化中起什么作用？ 2. 光感受器或 Muller 细胞中的 gp130 表达是否负责神经保护和功能丧失？ 3. PI3K/Akt 通路是否负责 gp130 诱导的神经保护作用？