Photoreceptor integration via chemotactic honing

 描述(申请人提供)：由于疾病或创伤导致的渐进性光感受器丧失导致美国各地不可逆转的失明。干细胞来源的光感受器移植为恢复视力提供了令人兴奋的潜力，但最主要的挑战是在复杂的视网膜结构中实现功能整合。令人惊讶的是，视网膜运动环境在移植的光感受器前体细胞(PPC)的定位和整合中的作用在很大程度上仍未被探索。我们的研究小组已经报道，PPC亚群对来自EGF和SDF-1的剂量依赖信号表现出不同的迁移反应：这些分子众所周知地激活受体介导的趋化作用，并在成人视网膜板层中大量存在。我们的假设是，通过选择能够在受损视网膜的复杂微环境中进行化学导航的亚群，PPC的整合将得到改善。该项目将培育一种独特的微流体和外植体视网膜模型的组合，以使具有打磨迁移能力的PPC(HM-PPC)能够选择性地适应光损伤视网膜中存在的一系列浓度梯度(作为模型)。然后，实验将评估HM-PPC群体在视网膜板层中整合的程度。

 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.