Regulation of neural stem cells in retina regeneration

描述（由申请人提供）：老年性黄斑变性（AMD）和糖尿病视网膜病变是导致视网膜神经退化的疾病，是65岁以上人群失明的两大主要原因。视网膜组织再生可能是治疗视力丧失的一种可能的方法，它将大大提高许多老年人的生活质量。发育中的雏鸡有能力再生完整的神经视网膜，以应对眼睛前缘的神经视网膜干细胞/祖细胞群的损伤。两种分泌蛋白，Wnt和BMP，已被证明可以激活对视网膜、脑和脊髓的神经干/祖细胞的增殖、分化和维持至关重要的信号通路。在发育过程中，这两种途径的分子都在鸡眼的前缘表达，因此可能在调节该区域的神经视网膜干/祖细胞中发挥作用。Aim 1的研究旨在通过原位杂交、RTPCR、免疫组织化学和Western blotting来确定胚胎鸡视网膜再生过程中Wnt和BMP信号通路关键分子的表达模式。Aim 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/祖细胞的作用，在发育中的鸡眼视网膜损伤诱导后，使用逆转录病毒载体激活或抑制这些通路。Aim 3旨在利用从特定aims 1和2中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/干细胞的激活，这些细胞通常缺乏或再生能力降低。本研究结果将极大地促进神经再生生物学领域的发展，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.