Photoreceptor integration via chemotactic honing

通过趋化珩磨实现光感受器整合

基本信息

批准号：
9225221
负责人：
MARIBEL VAZQUEZ
金额：
$ 19.63万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9225221
关键词：
Address Adult Architecture Biocompatible Materials Biological Assay Blindness Bolus Infusion CXCR4 gene Cell Transplants Cell physiology Cells Chemotaxis Ciliary Neurotrophic Factor Communication Complex Differentiation Antigens Disease Dose EGF gene Environment Exhibits Failure Fibroblast Growth Factor Genes Genetic Fingerprintings Glutamates Injection of therapeutic agent Ligands Light Measurement Measures Mediating Microfluidics Modeling Molecular Profiling Monitor Morphology Nature Nuclear Outcome Photoreceptors Population Positioning Attribute Reporting Reproducibility Retina Retinal Retinal Cone Retinal Diseases Role Signal Transduction Signaling Molecule Source Stem cell transplant Stem cells Stromal Cell-Derived Factor 1 Synapses System Testing Time Tissues Transplantation Trauma United States Vision Visual Wild Type Mouse base calcium indicator cell motility dosage experimental study follow-up improved injured migration neurotransmission notch protein novel phenotypic biomarker photoreceptor progenitor precursor cell public health relevance receptor receptor expression response retinal progenitor cell retinal rods synaptogenesis

项目摘要

DESCRIPTION (provided by applicant): Progressive photoreceptor loss due to disease or trauma leads to irreversible blindness throughout the USA. Transplantation of photoreceptors derived from stem cells offers exciting potential for restoring vision, but the overarching challenge is to achieve functional integration within the complex retinal architecture. Surprisingly, the role of the retinal motogenic environment in the positioning and integration of transplanted photoreceptor precursor cells (PPCs) remains largely unexplored. Our group has reported that PPC subsets exhibit distinct migratory responses to dose-dependent signaling from EGF and SDF-1: These molecules are well-known to activate receptor-mediated chemotaxis and are abundant in adult retinal laminae. It is our hypothesis that PPC integration will be improved by selectivity for subpopulations able to chemotactically navigate the complex microenvironments of damaged retina. This project will cultivate a unique combination of microfluidics and explant retina models to enable selectivity for PPCs with honing migratory capabilities (HM-PPCs) to a range of concentration gradients present in light-damaged retina (as a model). Experiments will then evaluate the extent to which HM- PPCs populations integrate within retinal laminae.

描述（由适用提供）：由于疾病或创伤引起的渐进感光受体丧失导致整个美国的不可逆失明。从干细胞中得出的感光体的移植为恢复视觉提供了令人兴奋的潜力，但是总体挑战是在复杂的残留体系结构中实现功能整合。令人惊讶的是，残留动物环境在移植光感受器前体细胞（PPC）的定位和整合中的作用在很大程度上仍然是出乎意料的。我们的小组报告说，PPC子集暴露了来自EGF和SDF-1剂量依赖性信号的不同迁移反应：这些分子是众所周知的，众所周知，可以激活受体介导的趋化性，并且在成年视网膜层中很丰富。我们的假设是，通过选择性跨越损坏的视网膜的复杂微环境的亚种群的选择性将提高PPC整合。该项目将培养微流体和外浮体视网膜模型的独特组合，以使PPC具有磨练的迁移能力（HM-PPC）的选择性，以使其在轻损伤的视网膜中存在的一系列浓度梯度（作为模型）中。然后，实验将评估HM-PPCS种群在视网膜层中整合的程度。