Cytokine Regulation of Photoreceptor Gene Expression

光感受器基因表达的细胞因子调节

• 批准号: 7583933
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583933
• 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; 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; inherited retinal degeneration; 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

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?

神经细胞因子在预防或延缓失明方面显示出巨大的治疗潜力。 这些细胞因子中的几种刺激受体gp 130。白血病抑制因子刺激 (LIF)睫状神经营养因子（CNTF）对视网膜细胞有三种深刻的影响：抑制视网膜细胞的生长， 分化;对视网膜变性的神经保护;以及光感受器的光反应降低。 尽管人们对这些作用感兴趣，但对gp 130在正常视网膜发育中的作用知之甚少， 其在防止感光细胞死亡中的作用。在这项研究中，我们将使用组织特异性的gp 130失活， 解决三个重要问题。1. gp 130在视网膜正常分化中的作用是什么？2. 光感受器或Muller细胞中gp 130的表达是否负责神经保护和功能 损失？3. PI 3 K/Akt通路是否负责gp 130诱导的神经保护作用？