Muller glia and retina regeneration

描述(申请人提供)：视网膜退化是西方世界最常见的致盲原因。超过5%的人口在他们一生中的某个时候会遭受视网膜变性的折磨。尽管我们在识别导致大量视网膜变性的基因方面取得了很大进展，但修复病变视网膜的策略仍然难以捉摸。最近的研究表明，哺乳动物的视网膜含有能够修复丢失的神经元的祖细胞，尽管效率非常低。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，以促进病变或受损视网膜的修复。斑马鱼等模型系统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，Muller胶质细胞参与了这一过程。我们研究的长期目标是确定穆勒胶质细胞在斑马鱼视网膜再生中所起的作用，并确定这些细胞促进视网膜修复的机制。最终，人们希望将这些信息应用于哺乳动物的视网膜，以提高其再生能力。我们建议使用细胞和分子生物学相结合的方法来研究Muller胶质细胞在视网膜再生中所起的作用。具体地说，我们建议：1)确定穆勒胶质细胞是否参与再生视网膜中所有主要类型的视网膜细胞的再生；2)确定穆勒胶质细胞是否对成功的视网膜再生是必需的；3)确定视网膜损伤后赋予穆勒胶质细胞祖细胞地位的基因变化；以及4)确定在视网膜再生过程中a1T基因表达和穆勒胶质细胞去分化的机制。这些研究将为未来将穆勒胶质细胞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，鱼视网膜的损伤会引发再生反应，恢复失去的视觉功能。我们的研究旨在确定鱼类视网膜成功再生的机制。我们认为，这些机制可能会为改善受损或患病的哺乳动物视网膜的修复提供新的策略。

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.