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In vivo imaging of newt lens regeneration: Novel molecular, cellular and functional insights

蝾螈晶状体再生的体内成像：新颖的分子、细胞和功能见解

基本信息

批准号：
10250409
负责人：
Katia Del Rio-Tsonis
金额：
$ 17.52万
依托单位：
MIAMI UNIVERSITY OXFORD
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10250409
关键词：
Adult Animal Model Animals Biology Blood Vessels Cataract Custom Degenerative Disorder Development Dorsal Electron Microscopy Epithelial Cells Eye Fiber Fluorescence Functional Imaging Genetic Models Genome Goals Histologic Human Image Imagination Imaging technology Immunofluorescence Immunologic In Situ Hybridization Injury Interruption Iris Knowledge Laser Scanning Microscopy Lens Fiber Life Cycle Stages Mission Molecular Monophenol Monooxygenase Morphology Multimodal Imaging Natural regeneration Newts Notophthalmus viridescens Optical Coherence Tomography Organ Oxygen Pigment Epithelium Pigments Pleurodeles Process Public Health Research Research Personnel Resolution Technology Testing Time Tissues Transgenic Organisms United States National Institutes of Health Vesicle Work anterior chamber cellular imaging clinically significant density eye chamber imaging capabilities imaging modality imaging platform imaging system in vivo in vivo imaging injured insight lens lens capsule lens regeneration macrophage metabolic rate molecular imaging mutant novel tissue regeneration tool

项目摘要

Project Summary Regenerating a human organ as its original one remains a part of our imagination. However, newts have unique capabilities of regenerating most of their tissues and organs, even into adulthood, including the lens. If the newt lens is lost or injured, it regenerates from the dorsal iris. Lens regeneration has important clinical significance, but it is also an ideal process for studying tissue regeneration in general. Many ex-vivo technologies, such as histological analysis, can only show us a snapshot of the regeneration process from a specific point of view at a specific time point. However, lens regeneration is a dynamic process involving cellular, molecular and functional changes. We have been able to, for the first time, non-invasively acquire high-quality in vivo images during the process of lens regeneration with optical coherence tomography (OCT) by tracking a single newt for over a period of 40 days. More interestingly, OCT was able to image the fragile zonular fibers for the first time during this process. This has not been documented using histological/immunohistological analysis. In addition, the blood vessels in the iris stroma are also clearly visible. In this proposal, we will significantly advance the imaging technology currently available. We hypothesize that by integrating high-resolution OCT and confocal fluorescence laser scanning microscopy (CFLSM), in combination with the use of newts lacking pigments in the iris and lineage tracing transgenic newts, we will be able to in vivo image the molecular, cellular, and functional changes taking place during the process of lens regeneration. To achieve this, we will custom-build a multimodality imaging system with high resolution, sufficient imaging depth, and functional imaging capabilities. In the three aims proposed, we will reveal the detail process of lens regeneration, including lens vesicle formation, lens fiber differentiation, the development of the zonular fibers, the changes in iris vasculature and the dynamic distribution of macrophages using a combination of mutant and transgenic newts. After completing these aims, we will have established a new comprehensive imaging platform, that will allow researchers to in vivo track the process of lens regeneration in a single newt without interruptions and contribute critical information that can be used to understand cataract biology, zonulopathies and lens replacement where intact lens capsules are absent in humans

项目概要将人体器官再生为原来的器官仍然是我们想象力的一部分。然而，蝾螈具有再生大部分组织和器官的独特能力，甚至可以再生为成年期，包括镜头。如果蝾螈晶状体丢失或受伤，它会从背虹膜再生。晶状体再生具有重要的临床意义，同时也是研究的理想过程一般而言，组织再生。许多离体技术，例如组织学分析，只能向我们展示特定时间、特定角度的再生过程快照观点。然而，晶状体再生是一个动态过程，涉及细胞、分子和功能变化。我们第一次能够非侵入性地获取高质量的光学相干断层扫描 (OCT) 晶状体再生过程中的体内图像通过对一条蝾螈进行 40 多天的跟踪。更有趣的是，OCT 能够成像在此过程中，脆弱的小带纤维首次受到损伤。这还没有被记录使用组织学/免疫组织学分析。此外，虹膜基质中的血管也清晰可见。在这项提案中，我们将显着推进目前的成像技术可用的。我们假设通过整合高分辨率 OCT 和共焦荧光激光扫描显微镜 (CFLSM)，结合使用蝾螈由于转基因蝾螈的虹膜和谱系缺乏色素，我们将能够在体内对过程中发生的分子、细胞和功能变化进行成像晶状体再生。为了实现这一目标，我们将定制一个多模态成像系统高分辨率、足够的成像深度和功能性成像能力。在三个目标中提出，我们将揭示晶状体再生的详细过程，包括晶状体囊泡的形成，晶状体纤维分化、小带纤维的发育、虹膜脉管系统的变化以及使用突变体和转基因组合的巨噬细胞的动态分布蝾螈。完成这些目标后，我们将建立一个新的综合影像平台，这将使研究人员能够在体内追踪晶状体再生的过程蝾螈不间断地贡献可用于理解的关键信息白内障生物学、小带病和晶状体置换术（其中缺乏完整的晶状体囊）人类