Regulation of neural stem cells in retina regeneration

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）和糖尿病视网膜病变是导致神经视网膜退化的疾病，是65岁以上人群失明的两个主要原因。视网膜组织的再生可能是视力丧失的一种可能的治疗方法，这将大大改善许多老年人的生活质量。发育中的小鸡有能力再生一个完整的神经视网膜，以响应来自眼前缘的神经视网膜干细胞/祖细胞群的损伤。两种分泌的蛋白质，Wnt和BMP，已被证明激活重要的增殖，分化和维持视网膜，脑和脊髓的神经干细胞/祖细胞的信号通路。来自这两种途径的分子在发育过程中在鸡眼的前缘中表达，因此可能在调节该区域中存在的神经视网膜干/祖细胞中发挥作用。目的1通过原位杂交、RT-PCR、免疫组化和Western blotting等方法，研究了鸡胚视网膜再生过程中Wnt和BMP信号通路中关键分子的表达模式。目的2旨在确定Wnt和BMP信号通路在视网膜再生过程中调节神经视网膜干/祖细胞中的作用，通过在发育中的鸡眼中诱导视网膜损伤后使用逆转录病毒载体激活或抑制这些通路。目的3旨在使用从特定目的1和2获得的信息来诱导或增加在更成熟的眼睛中发现的神经视网膜祖细胞/干细胞的活化，这些细胞通常缺乏再生能力或再生能力降低。这项研究的结果将大大增强神经再生生物学领域，并可能导致新的治疗药物或治疗AMD和糖尿病视网膜病变以及其他神经退行性疾病，如阿尔茨海默病和帕金森病。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) and diabetic retinopathy are diseases that lead to deterioration of the neural retina and two major causes of blindness in those over 65. Regeneration of retinal tissue may be a possible treatment for vision loss that would greatly improve the quality of life for many elderly individuals. The developing chick has the ability to regenerate a complete neural retina in response to injury from a population of neural retina stem/progenitor cells present in the anterior margin of the eye. Two secreted proteins, Wnt and BMP, have been shown to activate signaling pathways important for proliferation, differentiation and maintenance of neural stem/progenitor cells of the retina, brain, and spinal cord. Molecules from both of these pathways are expressed in the anterior margin of the chick eye during development and may therefore play a role in the regulating the neural retina stem/progenitor cells present in this region. Studies in Aim 1 are designed to determine the expression pattern of key molecules in the Wnt and BMP signaling pathways during retina regeneration in the embryonic chick via in situ hybridization, RTPCR, immunohistochemistry and Western blotting. Aim 2 is designed to determine the role the Wnt and BMP signaling pathways play in regulating neural retina stem/progenitor cells during retina regeneration by either activating or inhibiting such pathways using retroviral vectors after retinal damage is induced in the developing chick eye. Aim 3 is designed to use the information obtained from specific aims 1 and 2 to induce or increase the activation of neural retina progenitor/stem cells found in more mature eyes which would normally lack or have a reduced ability to regenerate. The results of this study will greatly enhance the field of neural regenerative biology and may lead to new therapeutic drugs or treatment for AMD and diabetic retinopathy as well as other neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.