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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

项目总结