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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

基本信息

批准号：
10203990
负责人：
ANDY J FISCHER
金额：
$ 38.82万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203990
关键词：
Acute B-Cell Activation Biological Models Blood Chick model Communication Complex Data Degenerative Disorder Development Disease Enhancers Genetic Glaucoma Goals Growth Factor Histone-Lysine N-Methyltransferase Homeostasis Homologous Gene Light MAP Kinase Gene Macular degeneration Mediating Molecular Muller&apos s cell Natural regeneration Nerve Regeneration Neuraxis Neuroglia Neuronal Differentiation Neurons Nuclear Pathway interactions Pharmacology Phenotype Polycomb Proliferating Regenerative capacity Reporting Retina Retinal Degeneration Retinal Diseases Rodent Model Role Signal Pathway Signal Transduction Source Vertebrates Vision cold blooded vertebrate experimental study gene repression genetic approach human disease in vivo insight mouse model neurodevelopment neurogenesis neuroinflammation neuron loss neuronal survival notch protein novel novel therapeutics progenitor regeneration potential repaired retinal damage retinal neuron retinal progenitor cell retinal regeneration stem cells

项目摘要

Project Summary: There is a rapidly growing body of evidence that Müller glia can are a source of retinal progenitors to promote neural regeneration. Many studies have demonstrated that Müller glia can become proliferating progenitor cells in the retinas of different vertebrate species. Most reports have studied Müller glia-derived progenitors in acutely damaged retinas. However, little is known about the mechanisms that stimulate neurogenesis from Müller 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 Müller glia-derived progenitors is crucially important to developing new therapies to treat degenerative diseases of the human retina. We have obtained compelling novel preliminary data indicating that cell-signaling through the nuclear factor kappa-light- chain-enhancer of activated B cells (NFκB) and the activity of Enhancer of Zeste Homolog 2 (EZH2) impacts the de-differentation and reprogramming of Müller glia into proliferating, neurogenic retinal progenitors. We will investigate how the phenotype and plasticity of the Müller glia are regulated by NFκB and EZH2 in normal, damaged and growth factor-treated retinas. We will use a combination of pharmacological and genetic approaches to selectively activate or inhibit NFκB and EZH2 in Müller glia. We will compare and contrast how NFκB-signaling and EZH2-acitvity impact the formation of Müller glia-derived progenitors in chick and rodent model systems with different inherent capacities for retinal regeneration. We expect that the completion of the experiments described in this proposal will provide significant new information regarding how NFκB and EZH2 influence mature Müller glia, the formation of Müller glia-derived progenitors and regeneration of retinal neurons. Identification and understanding of the mechanisms that enhance the neurogenic potential of Müller glia is required to develop new therapies for sight-threatening diseases, such as glaucoma and macular degeneration that involve the loss of retinal neurons.

项目总结：越来越多的证据表明，神经胶质细胞是视网膜的来源之一