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Molecular Generators at Corneal Wounds Produce and regulate the Wound Electrical Signals

角膜伤口处的分子发生器产生并调节伤口电信号

基本信息

批准号：
9892012
负责人：
Min Zhao
金额：
$ 39.25万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892012
关键词：
Active Ion Transport Address Affect Awareness Binding Cells Charge Chronic Cornea Corneal Injury Cues Data Defect Development Diabetes Mellitus Disease Electric Stimulation Electrical Resistance Electrophysiology (science)Environment Epithelial Epithelial Cells Epithelium Exhibits Generations Glean Glucose Goals Hour Human Impaired healing Impairment In Vitro Injury Insurance Ions Knowledge Metabolic Methods Modeling Molecular Molecular Genetics Muscle Natural regeneration Nature Nerve Organ Culture Techniques Organism Oxygen Pharmacologic Substance Physiologic pulse Physiological Regulation Research Rest Role Signal Transduction Site Tissues United States Centers for Medicare and Medicaid Services Wound models bioelectricity chronic wound clinical application corneal epithelial wound healing corneal epithelium diabetic diabetic ulcer diabetic wound healing electric field electrical potential experimental study healing high throughput screening improved in vivo insight mathematical model mechanical force migration millisecond non-diabetic non-healing wounds novel novel therapeutic intervention response segregation small molecule spatiotemporal tissue culture uptake vector wound wound healing

项目摘要

Abstract (Description) Live and intact cornea maintains an electric potential difference across the epithelium, the transepithelial potential difference (TEP). The compromised epithelial barrier in corneal wounds collapses the transepithelial potential at the wound site, resulting in naturally occurring endogenous electric fields that point towards the wound center from adjacent intact tissues. These naturally occurring wound electric fields (wEFs) provide powerful signals that stimulate and guide cells to migrate into the wound to initiate healing. We demonstrated that these electrical signals could override other directional cues, such as injury stimulation, free edge and mechanical forces, in guiding migration of corneal epithelial sheets and large groups of cells. Our long term goal is to elucidate the molecular mechanisms that generate and regulate the wound electric fields, i.e. to discover the “molecular generators”, and to use this knowledge to develop new therapeutic strategies to collectively mobilize cells (tissues) to heal chronic wounds and non-healing wounds. Our previous research has identified key ionic mechanisms and “molecular generators” that produce and regulate wEFs. Importantly, we demonstrated in three diabetic models that wEFs are defective and this correlates very well with impaired healing. Using high throughput screens, we also identified novel molecular mechanisms directing the responses of human corneal epithelial cells (CECs) to physiological electric fields. In this application, we will dissect the defective electrical signaling and impaired responses of epithelial cells in diabetic cornea. We therefore propose a comprehensive study to (1) elucidate ionic mechanisms underlying defective electrical signaling in diabetic corneal wounds, and to build a mathematical model that simulates wound electric fields; (2) determine how high glucose and oxygen uptake regulate electrogenic machinery, and how these mechanisms are impaired in diabetic cornea. Through completion of these aims, our goal is Aim (3) to electrically facilitate healing of diabetic wounds by correcting defects in generation of electrical signals.

文摘(描述)