Stimulation of retinal regeneration

刺激视网膜再生

• 批准号: 8076038
• 负责人: THOMAS A REH
• 金额: $ 37.64万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8076038
• 关键词: Adult; Affect; Amacrine Cells; Amphibia; Animals; Antibodies; Area; Birds; Blood; Brain; Bromodeoxyuridine; Cells; Complete Blindness; Data; Degenerative Disorder; Development; Disease; Elements; Engineering; FGF2 gene; Fishes; Gene Expression; Genes; Goals; Growth Factor; Human; IGF1 gene; In Vitro; Inherited; Injury; Lead; Left; Mammals; Molecular; Morphology; Mus; N-Methylaspartate; Natural regeneration; Nervous system structure; Neuroglia; Neurons; Pathway interactions; Pattern; Positioning Attribute; Publishing; Recovery; Regenerative Medicine; Relative (related person); Reporting; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Rodent; Sensory; Signal Pathway; Signal Transduction; Source; Testing; Transplantation; Vertebrates; Viral; Visual; Visual impairment; Zebrafish; advanced disease; base; calretinin; cell type; comparative; inherited retinal degeneration; inhibitor/antagonist; mouse model; novel strategies; programs; regenerative; repaired; research study; response; response to injury; restoration; retinal damage; retinal neuron; retinal progenitor cell; retinal regeneration; transcription factor

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.

描述（由申请人提供）：与神经系统的其他区域一样，视网膜受到许多获得和遗传的神经元变性疾病的约束。由于视网膜为大脑提供了所有视觉感觉信息的输入，因此细胞的损失会导致视觉障碍和潜在的完全失明。许多视网膜退行性疾病仅影响视网膜细胞的一部分，尽管在更晚期的疾病中经常会发生整个视网膜的损失和重组。长期以来，人们一直认为在人类中没有退化的细胞恢复。但是，现在有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组成部分也存在于哺乳动物中。在鱼类损伤后，所有类型的新神经元在穆勒胶质细胞中再生，并在功能上将其整合到现有电路中。在鸟类和啮齿动物中，再生在鸟类和啮齿动物的数量和类型的神经元中都受到更大的限制。尽管这可能代表同性热脊椎动物中的残留脊椎动物的残留再生反应，而其冷血的亲属，但在所有脊椎动物视网膜中都存在于再生的细胞来源Muller Glia。我们最近发布的数据和新的初步未发表的数据表明，穆勒胶质细胞的再生反应可能受到抑制剂激活基因表达的神经发生模式的限制。在此提案中，我们概述了测试有关限制哺乳动物视网膜中Muller Glia的因素的特定假设的实验。这些实验的结果将更好地理解哺乳动物Muller Glia的再生潜力的局限性，并可能导致发展新型策略来治疗人类视网膜变性。 公共卫生相关性：与神经系统的其他领域一样，视网膜受到许多获得和遗传的神经元变性疾病的约束。由于人们不会发生新的视网膜神经元的再生，因此这些疾病可能会使它们永久视觉障碍。在这项建议中，我们概述了实验，以更好地理解哺乳动物Muller Glia的再生潜力的局限性，这可能会导致发展新型策略以治疗人类视网膜退化。