Development and Regeneration of Retinal Ganglion Cells in the Vertebrate Retina

项目摘要/摘要 视力丧失是一种毁灭性的医疗问题，直接和间接地产生巨大的医疗成本 间接的形式是生产力下降，生活质量下降，以及这些人失去独立性 受影响。在美国，眼疾会给社会带来巨大的经济负担。因为 人的视网膜具有极低的再生能力或没有再生能力，由于固有缺陷或 环境侮辱通常是不可逆转的，这使这成为永久视觉的最常见原因 减损。在这个项目中，候选人建议研究视网膜神经节细胞的发育， 输出连接眼睛和大脑的投射神经元。这些神经元很容易受到损伤 外伤性视神经损伤和青光眼等疾病，以及对其更深层次的了解 发育和再生可能对逆转视力损害具有重要意义。在第一个 作为这项申请的一部分，候选人建议研究一种转录因子的功能 在小鼠视网膜神经节细胞系中有条件地删除了该基因，并通过在 体内的视网膜祖细胞。在本申请的第二部分，应聘者建议筛选一个 体内过表达的转录因子对内源性视网膜重新编程能力的候选列表 细胞产生新的视网膜神经节细胞。总体而言，来自正常视网膜神经节细胞研究的见解 开发将应用于开发当这些细胞受损或患病时替换它们的方法。 候选人的总体职业目标是了解塑造神经系统的发育过程， 并将这种发育知识应用于再生因损伤或疾病而失去的神经元。候选人有 深厚的大脑皮层发育生物学背景，建议接受视网膜方面的培训 开发是因为视网膜更易于临床操作，而且前景看好 再生疗法已经开始结出硕果。在该奖项的指导阶段， 应聘者将优先开展活动以增加对视网膜发育的了解， 多产和有意义的科学，从而使研究从大脑皮层发育过渡到 对视网膜发育的影响。国际和平协会将与导师杰弗里·戈德堡博士和王穗博士合作，以及 斯坦福大学教职员工顾问团队的成员。拟议的研究和培训计划将在 杰弗里·戈德堡博士的实验室，他是斯坦福大学眼科系主任 医学。斯坦福大学杰出的视觉科学小组嵌入了世界级的神经科学 作为一个整体，斯坦福大学更广泛的生命科学界，得益于紧密和专注的 系和更广泛的大学的资源。

Project Summary/Abstract Vision loss is a devastating medical problem that generates significant medical costs, directly as well as indirectly in the form of decreased productivity, lower quality of life, and loss of independence among those affected. In the United States, disorders of the eye result in a significant economic burden for society. Because the human retina has minimal or no regenerative ability, loss of retinal neurons due to intrinsic defects or environmental insults is generally irreversible, making this the most common cause of permanent visual impairment. In this project, the candidate proposes to study the development of retinal ganglion cells, the output projection neurons that connect the eye with the brain. These neurons are vulnerable to injury in traumatic optic nerve injuries and to diseases such as glaucoma, and a deeper understanding of their development and regeneration could have significant implications for reversing visual impairment. In the first part of this application, the candidate proposes to investigate the function of a transcription factor expressed by retinal ganglion cells in a mouse line with this gene conditionally deleted, and by using overexpression in retinal progenitor cells in vivo. In the second part of this application, the candidate proposes to screen a candidate list of transcription factors by overexpression in vivo for their ability to reprogram endogenous retinal cells to produce new retinal ganglion cells. Overall, insights from the study of normal retinal ganglion cell development will be applied to develop methods for replacing these cells when they are damaged or diseased. The candidate’s overall career goal is to understand developmental processes that shape the nervous system, and to apply this developmental knowledge to regenerate neurons lost to injury or disease. The candidate has a deep background in cerebral cortical developmental biology and proposes to receive training in retinal development because the retina is significantly more accessible to clinical manipulation, and promising regenerative therapies are already beginning to come to fruition. During the mentored phase of this award, the candidate will prioritize undertaking activities to increase understanding of retinal development, to do productive and meaningful science, and consequently to transition research from cerebral cortical development to retinal development. The PI will work with mentors Dr. Jeffrey Goldberg and Dr. Sui Wang, together with members of a Stanford faculty advisory team. The proposed research and training plans will take place in the laboratory of Dr. Jeffrey Goldberg, chair of the Department of Ophthalmology at Stanford University School of Medicine. The outstanding vision science group at Stanford is embedded within the world-class neuroscience and broader life sciences community at Stanford as a whole, with benefits of a close-knit and focused department and the resources of the wider university.