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TRP-CHANNELS IN LENS DEVELOPMENT AND CATARACT

TRP 通道在晶状体发育和白内障中的作用

基本信息

批准号：
10557158
负责人：
Alan Shiels
金额：
$ 38.09万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10557158
关键词：
AA Spectrophotometry Actins Address Agonist Alternative Splicing Anterior Arizona Bioinformatics Calcium Calcium Channel Cataract Cations Cell Line Cells Ciliary Body Clinical Collaborations Complement Cytoplasm Defect Deposition Development Disease Epithelial Cells Epithelium Eye Eye Development Eye diseases Functional disorder Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Genetic study Genome Glaucoma Goals Growth Homeostasis Human Image Imaging Techniques Immune response Immunofluorescence Microscopy Impairment Inherited Investigation Iris Knock-in Mouse Knockout Mice Knowledge Lens development Light Measures Membrane Messenger RNA MicroRNAs Molecular Mus Mutate Mutation Operative Surgical Procedures Optics Osmosis Pain Perception Physiological Processes Physiology Play Property Protein Isoforms RNA RNA Splicing Research Risk Factors Role Scientific Advances and Accomplishments Signal Pathway Smooth Muscle Steroids Stimulus Stress Symptoms TRP channel Techniques Technology Temperature Testing Therapeutic Tissues Transcript Transfection Universities Variant Visual impairment Water age related antagonist calcium phosphate childhood cataract deep sequencing epithelial to mesenchymal transition imaging facilities insight interdisciplinary approach lens lens morphogenesis lens transparency live cell imaging member mutant novel pressure preventive intervention receptor recruit response transcription factor transcriptome sequencing vision development

项目摘要

Project Summary/Abstract The transient receptor potential (TRP) superfamily of non-selective cation channels play critical roles in diverse physiological processes including the perception of light, temperature, pressure, and pain. In previous genetic studies, we have discovered that mutation of a member of the melastatin-related TRP-channels (TRPM3) underlies an inherited form of pediatric cataract that is variably associated with glaucoma and anterior segment defects. In this proposal, we will investigate the role of TRPM3 in lens development and cataract pathobiology using gene-edited mice and cell-lines by addressing three specific aims. In aim-1, we will characterize lens TRP-channel transcript splice-variants by means of RNA deep-sequencing and the calcium channel properties of lens TRPM3 isoforms using fluorometric calcium imaging techniques. In aim-2, we will characterize the effects of TRPM3 dysfunction and deficiency on lens cation status, water content, and calcium influx properties using a combination of atomic absorption spectrometry and calcium imaging techniques. In aim-3, we will characterize the effects of TRPM3 dysfunction and deficiency on lens morphogenesis and gene expression using differential immuno-fluorescence microscopy and RNA deep-sequencing techniques, respectively. Results from these studies will provide new insights regarding the role of TRP-channels in lens growth, cation homeostasis, calcium dynamics, and pathophysiology within the context of pediatric cataract – a clinically important risk factor for lifelong visual impairment. More broadly, these studies will contribute to an understanding of TRP-channel function and dysfunction in other eye tissues (e.g., iris, ciliary body) and diseases (e.g., glaucoma, anterior eye defects), respectively.

项目总结/文摘