Stimulation of retinal regeneration

描述（由申请人提供）：与神经系统的其他区域一样，视网膜易患许多获得性和遗传性神经元退行性疾病。由于视网膜为大脑提供所有视觉感官信息的输入，因此细胞的损失导致视觉障碍和潜在的完全失明。许多视网膜变性疾病仅影响视网膜细胞的子集，尽管在更晚期的疾病中，经常会发生整个视网膜的丢失和重组。长期以来，人们一直认为在人类中，退化的细胞无法恢复;然而，现在越来越多的证据表明，哺乳动物视网膜的神经元再生能力有限，并且在非哺乳动物脊椎动物中发现的再生反应的某些成分也存在于哺乳动物中。在鱼类中，视网膜损伤后，所有类型的新神经元都从Muller胶质细胞中再生出来，它们在功能上整合到现有的电路中。鸟类和啮齿类动物的神经元再生在数量和类型上都受到相当大的限制。虽然这可能代表了恒温脊椎动物与其冷血亲属相比时的退化再生反应，但Muller胶质细胞（再生的细胞来源）存在于所有脊椎动物视网膜中。我们最近发表的数据和新的初步未发表的数据表明，穆勒神经胶质细胞的再生反应可能是有限的抑制剂在其激活的神经原性模式的基因表达。在这个建议中，我们概述了实验来测试特定的假设的因素，限制再生的穆勒神经胶质细胞在哺乳动物视网膜。这些实验的结果将提供一个更好的了解哺乳动物穆勒神经胶质细胞的再生潜力的限制，并可能导致开发新的策略来治疗人类视网膜变性。 与神经系统的其他区域一样，视网膜也会受到许多获得性和遗传性神经退行性疾病的影响。由于新的视网膜神经元的再生不会发生在人身上，这些疾病可能会给他们留下永久性的视力障碍。在这个建议中，我们概述了实验，以提供更好地了解哺乳动物穆勒神经胶质细胞的再生潜力的限制，这可能会导致开发新的策略，用于治疗人类视网膜变性。

DESCRIPTION (provided by applicant): Like other areas of the nervous system, the retina is subject to many acquired and inherited neuronal degenerative diseases. Since the retina provides the input for all visual sensory information to the brain, the loss of cells results in visual impairment and potentially complete blindness. Many retinal degenerative diseases affect only a subset of the retinal cells, although, frequently in more advanced disease, loss and reorganization of the entire retina can occur. It has long been thought that in humans there is no recovery of the degenerated cells; however, there is now increasing evidence that the mammalian retina has a limited capacity for neuronal regeneration, and some components of the regenerative response found in non-mammalian vertebrates are also present in mammals. In fish, new neurons of all types regenerate from Muller glia following retinal damage and they are functionally integrated into the existing circuitry. Regeneration is considerably more limited in birds and rodents, both in quantity and types of neurons generated. Although this may represent a vestigial regenerative response in homoeothermic vertebrates when compared with their cold- blooded relatives, Muller glia, the cellular source for regeneration, are present in all vertebrate retinas. Our recently published data and new preliminary unpublished data indicate that the regenerative response of Muller glia might be limited by inhibitors in their activation of a neurogenic pattern of gene expression. In this proposal we outline experiments to test specific hypotheses about the factors that limit regeneration from the Muller glia in the mammalian retina. The results of these experiments will provide a better understanding of the limits of the regenerative potential of mammalian Muller glia, and may lead to development of novel strategies for treatment of human retinal degeneration. PUBLIC HEALTH RELEVANCE: Like other areas of the nervous system, the retina is subject to many acquired and inherited neuronal degenerative diseases. Since regeneration of new retinal neurons does not occur in people, these diseases can leave them with permanent visual impairment. In this proposal we outline experiments to provide a better understanding of the limits of the regenerative potential of mammalian Muller glia, which may lead to development of novel strategies for treatment of human retinal degeneration.