Cytokine Regulation of Photoreceptor Gene Expression

描述（由申请人提供）：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。这些细胞因子中的一些刺激受体gp130。白血病抑制因子（LIF）或睫状体神经营养因子（CNTF）刺激视网膜细胞有三个深刻的影响：抑制分化；视网膜变性的神经保护作用；减少了光感受器的光响应。尽管对这些影响感兴趣，但对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。在这项研究中，我们将使用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的作用是什么？2. gp130在感光细胞或Muller细胞中的表达是神经保护和功能丧失的原因吗？3. PI3K/Akt通路是否参与gp130诱导的神经保护？

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?