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In vivo 2-photon imaging of retinal biochemistry before and after retinal organoid transplantation

视网膜类器官移植前后视网膜生物化学的体内2光子成像

基本信息

批准号：
10643273
负责人：
Andrew W Browne
金额：
$ 19.43万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10643273
关键词：
Adult Age Age related macular degeneration Animal Model Award Biochemical Biochemistry Biological Markers Biological Sciences Biology Biophotonics Bioreactors Blindness California Capital Cell Death Cell physiology Cells Cellular biology Cessation of life Chemistry Clinical Clinical Assessment Tool Collaborations Data Development Development Plans Disease Elderly Electrophysiology (science)Elements Engineering Ensure Equipment Exhibits Eye Eye diseases Fluorescence Fluorescence Microscopy Fostering Functional Imaging Functional disorder Future Gene Mutation Genetic Genetic Diseases Goals High Pressure Liquid Chromatography Histology Human IACUC Image Imaging Device Imaging Techniques Immunohistochemistry In Vitro Inflammation Investigation Knowledge Label Laboratories Laboratory Research Light Link Mentors Metabolic Metabolism Methods Microfluidics Microscope Modeling Molecular Molecular Analysis Molecular Profiling Monitor Multimodal Imaging Mus Mutation Operative Surgical Procedures Optics Organoids Phase Photoreceptors Physicians Population Procedures Protocols documentation Quality Control Rattus Recovery Rehabilitation therapy Replacement Therapy Reporter Reporter Genes Research Research Activity Research Personnel Resources Retina Retinal Degeneration Retinal Diseases Retinoids Scientist Source Structure of retinal pigment epithelium System Techniques Testing Therapeutic Time Tissue Transplantation Tissues Training Training Programs Training Support Transgenic Organisms Translating Translational Research Translations Transplantation Universities Vision Visual Visualization Work biomarker identification blind career career development cell replacement therapy cell type doctoral student engineered stem cells experience imaging biomarker imaging modality improved in vivo insight invention metabolic imaging mouse model next generation non-invasive imaging novel novel therapeutics optical imaging organoid transplantation pre-clinical research preclinical study preclinical trial predictive marker professor replacement tissue restoration retina transplantation retinal imaging skills stem cells success superior colliculus Corpora quadrigemina therapeutic candidate tissue culture tool transcriptomics transplantation therapy treatment response two-photon

项目摘要

Project Summary Candidate and Career Development Plan: Dr. Browne is an assistant professor practicing vitreoretinal surgery and functioning as an engineer and physician-scientist at the University of California, Irvine. Dr. Browne established his engineering and basic biological sciences skills as a PhD student. He has balanced clinical duties with his laboratory research activities and. His long-term career goals are to engineer functional imaging tools that will advance the understanding of early and advanced eye diseases and facilitate the therapies needed to treat humans. His training thus far has been using in vitro imaging alone. To achieve his career goals, he is requesting support for training to develop functional imaging tools in vivo and the molecular tools to correctly interpret Two-photon imaging (2PI) observations from animal models. This K08 award will enable Dr. Browne to develop his scientific and professional skills in advanced imaging, fluorescence microscopy, and retinal cellular biology applied in vivo. Dr. Browne and his co-mentors, Drs. Palczewski, Seiler and Kuppermann, have developed a hands-on strategy to fulfill the training requirements through relevant course work, didactics, laboratory techniques, and collaborations at UC Irvine. The training program will prepare Dr. Browne to submit R01-level proposals to independently investigate and optimize functional retinal imaging as a tool for therapeutic discovery. Research Plan: Many blinding retinal conditions, like age-related macular degeneration, are the consequence of biochemical dysfunction and the secondary effects of inflammation and cell death. Conventional clinical tools provide valuable structural information about the retina but are unable to visualize retinal function. Non-linear optical imaging can now reveal subcellular biochemistry in vitro and has emerged as a reliable tool to study retinal disease. 2PI in mouse models demonstrates subcellular changes in energy and light cycle metabolism. Cell replacement therapy has emerged as a therapeutic candidate for advanced vision loss, and preclinical trials in rats have demonstrated visual function restoration. To understand metabolic function in retinal organoids (RtOg) before and after transplantation into blind rats, we will employ functional 2PI in vitro and in vivo as outlined in the following specific aims. 1) Investigate RtOg maturation with 2PI and correlate functional imaging data with cell-specific reporters in vitro and molecular signatures post vivo, 2) Identify functional imaging biomarkers for in vivo metabolism using 2PI of normal rats and rat with retinal degeneration, 3) Study in vivo functional 2PI of transplanted RtOgs in rats to identify alterations in functional imaging biomarkers and correlate imaging findings with visual function testing. Completion of these aims will yield time-resolved metabolic detail for specific cell populations in developing RtOgs, avail novel in vivo information about retinal biochemistry in healthy retina, diseased retina, and diseased retinas treated with retinal sheet transplantation. These discoveries will guide future translation of both functional imaging and tissue replacement therapy in humans.