Cells and genes that govern inflammation in the subretinal space

摘要 杀死视网膜神经元或光感受器的损伤或疾病从源头上阻碍了视力。这个 视网膜不能修复是人类神经系统的一个特征；死亡的神经元不是 被替换且丢失的功能不会恢复。这一黯淡的结果是推动 神经干细胞和再生生物学领域的研究。这个项目的目标是 是进行新的探索性研究，研究新的概念和特征 新发现的细胞类型被认为在死亡和死亡过程中发挥关键作用 脊椎动物视网膜中光感受器的再生。这项工作将扩展我们实验室的项目 朝着新的方向前进。 这个研究项目利用了斑马鱼的视网膜，斑马鱼视网膜是唯一的脊椎动物中枢神经系统组织 内源性细胞可以再生单一类型的神经元，整合到现有的突触中 循环，或再生所有类型的细胞，可以完全恢复原始组织。 提出了两个具体的目标，每个目标都旨在揭示对细胞的重要见解 以及控制光感受器视网膜下间隙炎症的分子机制 死亡和再生。具体目标1将探讨RPE在建立 视锥细胞选择性死亡期间视网膜下间隙内的炎症情况 光感受器。特定目标2将建立一个新识别的转录签名 视网膜下小胶质细胞的数量，与RPE一样，与 光感受器。确定炎症反应如何调控光感受器 再生将促进我们对支配视网膜干的分子机制的了解 和祖细胞，并可能指导基于细胞的治疗视网膜损伤和疾病 在人类身上。

Abstract Injuries or diseases that kill retinal neurons or photoreceptors block vision at it source. The inability to repair the retina is a hallmark of the human nervous system; neurons that die are not replaced and functions that are lost are not recovered. This bleak outcome is a driving force for research on neural stem cells and the field of regeneration biology. The objective of this project is to undertake novel exploratory studies that will investigate new concepts and characterize newly-identified cell types that are hypothesized to play key roles during the death and regeneration of photoreceptors in the vertebrate retina. This work will extend projects in our lab toward new directions. This program of research utilizes the zebrafish retina, the only vertebrate CNS tissue in which endogenous cells can regenerate a single neuronal type, which integrates into existing synaptic circuits, or regenerate all cell types that can completely restore the original tissue. Two Specific Aims are proposed, each designed to reveal important insights into the cellular and molecular mechanisms that govern inflammation in subretinal space during photoreceptor death and regeneration. Specific Aim 1 will explore the role the RPE plays in establishing the inflammatory mileau within the sub-retinal space during the selective death of cone photoreceptors. Specific Aim 2 will establish the transcriptomic signature of a newly-identified population of subretinal microglia, which, like the RPE, have an exclusive relationship to photoreceptors. Determining how the inflammatory response governs photoreceptor regeneration will advance our knowledge of the molecular mechanisms that govern retinal stem and progenitor cells and may guide cell-based therapeis for treating retinal injuries and disease in humans.