Muller glia and retina regeneration

描述（由申请人提供）：视网膜变性是西方世界最常见的致盲原因。超过5%的人在他们生命中的某个时候会患有视网膜变性。虽然我们在确定导致视网膜变性的基因方面取得了很大进展，但修复患病视网膜的策略仍然难以捉摸。最近的研究表明，哺乳动物的视网膜拥有祖细胞，可以恢复失去的神经元，尽管效率很低。神经生物学家研究视网膜的一个目标是确定诱导再生反应的策略，以促进患病或受损视网膜的修复。模型系统，如斑马鱼，在研究视网膜再生时提供了特殊的优势，部分原因是它们强大的再生能力。鱼类成功再生受损视网膜的机制尚不清楚，尽管我们最近提供的证据表明穆勒胶质细胞参与其中。我们研究的长期目标是确定Muller胶质细胞在斑马鱼视网膜再生中的作用，并确定这些细胞有助于视网膜修复的机制。最终，希望这些信息可以应用于哺乳动物视网膜，以提高其再生能力。我们建议使用细胞和分子生物学的方法相结合，以调查穆勒胶质细胞在视网膜再生中发挥的作用。具体而言，我们建议：1）确定Muller神经胶质是否介导再生视网膜中所有主要视网膜细胞类型的再生; 2）确定Muller神经胶质是否是成功视网膜再生所必需的; 3）鉴定视网膜损伤后赋予Muller神经胶质祖细胞状态的遗传变化;和4）鉴定视网膜再生期间a1 T基因表达和Muller神经胶质去分化的潜在机制。这些研究将为未来穆勒神经胶质作为鱼类和哺乳动物视网膜修复细胞来源的研究奠定基础。 与哺乳动物不同，鱼类视网膜的损伤会引发再生反应，可以恢复失去的视觉功能。我们的研究旨在确定鱼类成功视网膜再生的机制。我们认为这些机制可能为改善受损或患病哺乳动物视网膜的修复提供了新的策略。

DESCRIPTION (provided by applicant): Retinal degenerations are the most common cause of blindness in the Western world. Over 5% of the population will, at some point in their lives, suffer from retinal degeneration. Although we have made great strides in identifying genes responsible for much retinal degeneration, strategies for repairing the diseased retina have remained elusive. Recent studies suggest that the mammalian retina harbors progenitors that can restore lost neurons, albeit with very low efficiency. One goal of neurobiologists studying the retina is to identify strategies for inducing a regenerative response that would facilitate repair of the diseased or damaged retina. Model systems, like zebrafish, offer an exceptional advantage when studying retinal regeneration, in part because of their robust regenerative powers. The mechanism by which fish successfully regenerate a damaged retina is not known, although we recently provided evidence suggesting Muller glia are involved. The long term goal of our research is to ascertain the role Muller glia play in zebrafish retinal regeneration and identify the mechanisms by which these cells contribute to retinal repair. Ultimately it is hoped that this information can be applied to the mammalian retina to improve its regenerative ability. We propose to use a combination of cell and molecular biological approaches to investigate the role Muller glia play in retinal regeneration. Specifically we propose to: 1) Determine if Muller glia mediate regeneration of all major retinal cell types in the regenerating retina; 2) Determine if Muller glia are necessary for successful retina regeneration; 3) Identify the genetic changes that impart a progenitor status to Muller glia following retinal injury; and 4) Identify mechanisms underlying a1T gene expression and Muller glia dedifferentiation during retinal regeneration. These studies will form the foundation for future investigations of Muller glia as a source of cells for retinal repair in fish and mammals. Unlike mammals, injury to the fish retina initiates a regenerative response that can restore lost visual function. Our research aims to identify the mechanisms underlying successful retina regeneration in fish. We propose that these mechanisms may suggest new strategies for improving repair of the damaged or diseased mammalian retina.