Regulation of adult ciliary body progenitor cells for cell replacement therapy

细胞替代疗法中成人睫状体祖细胞的调节

基本信息

批准号：
8228143
负责人：
Sai Hemanth Chavala
金额：
$ 23.64万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2016-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8228143
关键词：
Ablation Address Adult Age related macular degeneration Aniridia Anophthalmos Applications Grants Atrophic Autologous Blindness Cell Lineage Cells Cellular biology Ciliary Body Clinical Collaborations Country Data Deterioration Development Ensure Epithelial Epithelial Cells Exudative age-related macular degeneration Eye Eye Development Foundations Funding Future Genetic Goals Human In Situ Hybridization In Vitro Injury Iris Lead Maintenance Mentors Mentorship Modeling Molecular Monitor Mus Mutation Pathway interactions Patients Photoreceptors Physicians Quality of life RNA Regulation Regulatory Pathway Replacement Therapy Reporter Research Retinal Retinal Pigments Reverse Transcriptase Polymerase Chain Reaction Role Scientist Source Specific qualifier value Stem cells Structure of retinal pigment epithelium Teratoma Testing Transgenic Mice Transgenic Organisms Undifferentiated United States United States National Institutes of Health Variant Vision Western World Work career cell type embryonic stem cell experience improved in vivo insight meetings mouse model multipotent cell neovascular prevent public health relevance research study restoration retinal neuron retinal progenitor cell stem tool transcription factor transdifferentiation tumor

项目摘要

DESCRIPTION (provided by applicant): Age-related macular degeneration (ARMD) is the leading cause of vision loss in the western world. Non-neovascular ("dry") ARMD is characterized by poorly functioning retinal pigment epithelial (RPE) cells. Strategies to replace damaged RPE cells may prevent vision deterioration. Adult ciliary body epithelial cells are a patient specific, multipotent cell source that can differentiate into cells that mimic RPE cells. We intend to investigate the regulatory pathways that guide adult ciliary body progenitor cell specification into an RPE lineage. SOX2 and PAX6 are transcription factors that are attractive candidates for regulating this pathway because they are essential for normal eye development and are expressed in retinal stem cells. We intend to use transgenic mouse models to ablate or express SOX2 and PAX6 to dissect the role of these transcription factors in progenitor cell biology. My long-term scientific goal is to develop a strategy to replace damaged RPE cells for patients with non-neovascular ARMD. This project will be completed in collaboration with Dr. Larysa Pevny, an expert stem cell scientist and developmental biologist, who has significant experience in studying SOX2 and PAX6 in retinal development. In her research, she has developed the genetic tools to answer the hypotheses in this proposal and has agreed to serve as my primary mentor for this project. Drs. Patterson, Meredith, and McGahan will provide career mentorship and monitor scientific progress for the duration of this grant proposal. Their purpose will be to ensure that I am meeting incremental goals on the way to becoming an independently NIH funded physician scientist. PUBLIC HEALTH RELEVANCE: We will utilize transgenic mice to study the transcriptional role and importance of SOX2 and PAX6 in adult ciliary body progenitor cells.

描述（由申请人提供）：与年龄相关的黄斑变性（ARMD）是西方世界视力丧失的主要原因。非血管（“干”）ARMD的特征是视网膜色素上皮（RPE）细胞功能较差。替代受损RPE细胞的策略可能会防止视力恶化。成年睫状体上皮细胞是一种患者特异性的多能源，可以区分模仿RPE细胞的细胞。我们打算研究将成年睫状体祖细胞规范引导到RPE谱系中的调节途径。 SOX2和PAX6是转录因子，是调节该途径的有吸引力的候选因子，因为它们对于正常的眼睛发育至关重要，并且在视网膜干细胞中表达。我们打算使用转基因小鼠模型消融或表达SOX2和PAX6，以剖析这些转录因子在祖细胞生物学中的作用。我的长期科学目标是制定一项策略，以替代非血管ARMD患者的RPE细胞受损。该项目将与专家干细胞科学家和发育生物学家Larysa Pevny博士合作完成，他在研究视网膜开发方面拥有SOX2和PAX6的丰富经验。在她的研究中，她开发了遗传工具来回答该提案中的假设，并同意担任该项目的主要导师。博士。帕特森（Patterson），梅雷迪思（Meredith）和麦加汉（McGahan）将在此赠款提案的期限内提供职业指导和监控科学进步。他们的目的是确保我实现成为独立NIH资助的医师科学家的途径的增量目标。公共卫生相关性：我们将利用转基因小鼠研究SOX2和PAX6在成人纤毛体祖细胞中的转录作用和重要性。