Muller glia: roles in retinal homeostasis and neuronal regeneration

Muller 胶质细胞：在视网膜稳态和神经元再生中的作用

• 批准号: 8511663
• 负责人: ANDY J FISCHER
• 金额: $ 36.22万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511663
• 关键词: Ablation; Acute; Birds; Blood; Canis familiaris; Cells; Communication; Data; Degenerative Disorder; Development; Disease; Gene Targeting; Generations; Glaucoma; Glucocorticoid Receptor; Goals; Homeostasis; Human; Ligands; MAP Kinase Gene; MAPK14 gene; Macular degeneration; Mediating; Microglia; Molecular; Natural regeneration; Nerve Regeneration; Neuroglia; Neurons; Primates; Proliferating; Publishing; Receptor Signaling; Replacement Therapy; Reporting; Retina; Retinal; Retinal Diseases; Rodent; Role; Signal Pathway; Signal Transduction; Source; Stem cells; Vertebrates; Vision; cold blooded vertebrate; insight; knock-down; neurogenesis; notch protein; progenitor; research study; response; retinal damage; retinal neuron; retinal progenitor cell; retinal regeneration

DESCRIPTION (provided by applicant): There is a rapidly growing body of evidence that Muller glia are a source of retinal progenitors to mediate neural regeneration. Many studies have demonstrated that Muller glia can become proliferating progenitor cells in the retinas of different vertebrate species. Nearly all reports have studied Muller glia-derived progenitors in acutely damaged retinas. However, little is known about the mechanisms that stimulate neurogenesis from Muller glia-derived progenitors in undamaged retinas or retinas undergoing slow, progressive degeneration. Furthermore, the regeneration of retinal neurons in warm-blooded vertebrates is limited compared to that seen in cold-blooded vertebrates. Therefore, the identification of the secreted factors and signaling pathways that permit and/or stimulate neural regeneration from Muller glia-derived progenitors is crucially important to developing new therapies to treat degenerative diseases of the human retina. We have obtained preliminary data indicating that signaling through the glucocorticoid receptor (GCR), p38 MAPK and signals derived from other types of retinal glia significantly impact the neurogenic potential of Muller glia. We will investigate the coordinated activity of different types of retinal glia including the Muller glia, microglia and the recently described Non-astrocytic Inner Retinal Glia-like (NIRG) cells. We have identified the NIRG cells as a distinct type of glial cell that is present in retina of birds, canines and primates. We believe that the NIRG cells influence the ability of Muller glia to become retinal progenitors. We expect that the completion of the experiments described in this proposal will provide significant new information regarding different signaling pathways, secreted factors, and how the microglia and NIRG cells influence the formation of Muller glia-derived retinal progenitors. Identification and understanding of the mechanisms that enhance the neurogenic potential of Muller glia is required to develop new therapies for sight-threatening diseases, such as glaucoma and macular degeneration that involve the loss of retinal neurons.

描述（由申请人提供）：有大量证据表明，穆勒神经胶质是介导神经再生的视网膜祖细胞的来源。许多研究表明，在不同脊椎动物的视网膜中，穆勒胶质细胞可以成为增殖的祖细胞。几乎所有报道都研究了急性损坏的视网膜中的穆勒胶质衍生的祖细胞。然而，对于未损坏的视网膜或视网膜中刺激穆勒神经胶质衍生的祖细胞的神经发生的机制知之甚少。此外，与冷血脊椎动物相比，温血脊椎动物中视网膜神经元的再生受到限制。因此，识别允许和/或刺激穆勒神经胶质衍生祖细胞神经再生的分泌因子和信号通路对于开发新的疗法以治疗人类视网膜的退行性疾病至关重要。我们已经获得了初步数据，表明通过糖皮质激素受体（GCR），p38 MAPK和来自其他类型的视网膜胶质的信号显着影响Muller Glia的神经发生潜力。我们将研究不同类型的视网膜神经胶质的协调活性 Muller Glia，小胶质细胞和最近描述的非核细胞内视网膜胶质样细胞（NIRG）细胞。我们已经将NIRG细胞确定为鸟类，犬和灵长类动物视网膜中存在的一种不同类型的神经胶质细胞。我们认为NIRG细胞会影响Muller Glia的能力 成为视网膜祖细胞。我们预计，本提案中描述的实验的完成将提供有关不同信号通路，分泌因素以及小胶质细胞和NIRG细胞如何影响穆勒胶质衍生的视网膜祖细胞形成的重要新信息。需要鉴定和理解增强Muller Glia神经源性潜力的机制，以开发新的危害视力疾病的疗法，例如涉及视网膜神经元丧失的青光眼和黄斑变性。