Contact Lens Wear, Bacteria, and Corneal Homeostasis

隐形眼镜佩戴、细菌和角膜稳态

基本信息

  • 批准号:
    10610842
  • 负责人:
  • 金额:
    $ 39.25万
  • 依托单位:
  • 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:
    2019-05-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Summary: Worn by >40 million people in the USA alone, contact lenses are associated with a risk of sight-threatening infection. With increasing use for myopia prevention and efforts to develop lenses for technological purposes, a surge in lens usage (extended wear specifically) is predicted. Unfortunately, research related to lens-related complications has been hindered by lack of an in vivo model amenable to the many research tools available only for mice. Following a 25-year effort, we have developed a mouse contact lens wear model. This utilizes silicone hydrogel lenses custom made by a contact lens manufacturer to fit mouse eyes, and does not require lid suturing. The lenses enable corneal infection when contaminated with P. aeruginosa, the most common causative agent of contact lens-related keratitis in people. Foundational to understanding contact lens related infection is knowing how a lens impacts the cornea without bacterial inoculation. Preliminary data show the mouse model replicates multiple events occurring during human lens wear, including colonization of the lens with commensal-type bacteria, and a dendritic cell (DC) response within 24 h. Moving beyond what is feasible using human subjects, high resolution time-lapse imaging of mice with fluorescent cell membranes revealed normally not present motile cells resembling neutrophils in the stroma after 6 days of wear. Immunohistochemistry confirmed infiltration of Ly6G+ cells (neutrophil marker). This DC/Ly6G+ response without pathology fits the definition of parainflammation as “a low-grade inflammatory response at an intermediate state between tissue homeostasis and classic inflammation which can be induced by persistent tissue stress…” The three aims of this project will explore; 1) triggers of parainflammation during contact lens wear, 2) how the signal is transduced within the cornea to drive the Ly6G+ cell response, and 3) its significance during microbe challenge. The hypothesis, based on published and preliminary data, is that parainflammation during contact lens wear in mice can be triggered by microbes colonizing the lens, initiating a sequence of events not otherwise occurring in the normally microbiome-free cornea that function to protect it against commensal-type bacteria, but which primes the cornea to respond overly-aggressively to P. aeruginosa. !
总结: 仅在美国就有超过4000万人佩戴隐形眼镜,隐形眼镜与视力威胁风险有关。 感染随着越来越多地用于预防近视和努力开发用于技术目的的镜片, 预计透镜使用(特别是长期佩戴)会激增。不幸的是,与镜片相关的研究 由于缺乏适用于许多可用研究工具的体内模型, 只有老鼠。经过25年的努力,我们已经开发出一个鼠标接触透镜磨损模型。这利用 由接触透镜制造商定制的硅水凝胶镜片,以适应小鼠眼睛,并且不需要盖子 - 是的当被铜绿假单胞菌污染时,这种镜片会导致角膜感染, 人接触镜相关角膜炎的病原体。 了解接触透镜相关感染的基础是了解透镜如何影响角膜,而不 细菌接种初步数据显示,小鼠模型复制了 人透镜配戴,包括用细菌型细菌和树突状细胞(DC)定殖所述透镜 24小时内回复超越了使用人类受试者的可行性,高分辨率延时摄影 具有荧光细胞膜的小鼠的成像显示正常情况下不存在类似于 在佩戴6天后,基质中的中性粒细胞。免疫组织化学证实Ly6G+细胞浸润 (中性粒细胞标志物)。这种无病理的DC/Ly6G+反应符合副炎症的定义,即"一种 处于组织稳态和经典状态之间的中间状态的低度炎症反应 持续的组织压力会引发炎症" 本项目的三个目标将探讨:1)接触透镜佩戴期间副炎症的触发因素,2) 信号在角膜内转导以驱动Ly6G+细胞应答,以及3)其在微生物培养期间的意义 挑战.根据已发表的和初步的数据, 小鼠的透镜磨损可由定植在透镜上的微生物触发,引发一系列事件,而不是其他情况 发生在正常无微生物群的角膜中,其功能是保护角膜免受角膜型细菌的侵害, 但这会使角膜对铜绿假单胞菌产生过度积极的反应。 !

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Topical antibiotics reduce CD11c+ cell numbers in the healthy murine cornea and modulate their response to contact lens wear.
  • DOI:
    10.1038/s41598-022-14847-x
  • 发表时间:
    2022-06-23
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Datta A;Lee J;Truong T;Evans DJ;Fleiszig SMJ
  • 通讯作者:
    Fleiszig SMJ
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Suzanne MJ FLEISZIG其他文献

Suzanne MJ FLEISZIG的其他文献

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{{ truncateString('Suzanne MJ FLEISZIG', 18)}}的其他基金

Contact Lens Wear, Bacteria, and Corneal Homeostasis
隐形眼镜佩戴、细菌和角膜稳态
  • 批准号:
    9762535
  • 财政年份:
    2019
  • 资助金额:
    $ 39.25万
  • 项目类别:
Contact Lens Wear, Bacteria, and Corneal Homeostasis
隐形眼镜佩戴、细菌和角膜稳态
  • 批准号:
    9920709
  • 财政年份:
    2019
  • 资助金额:
    $ 39.25万
  • 项目类别:
Contact Lens Wear, Bacteria, and Corneal Homeostasis
隐形眼镜佩戴、细菌和角膜稳态
  • 批准号:
    10396524
  • 财政年份:
    2019
  • 资助金额:
    $ 39.25万
  • 项目类别:
Corneal Infection: Role of Bacterial Adaptation
角膜感染:细菌适应的作用
  • 批准号:
    9316631
  • 财政年份:
    2014
  • 资助金额:
    $ 39.25万
  • 项目类别:
Corneal Infection: Role of Bacterial Adaptation
角膜感染:细菌适应的作用
  • 批准号:
    8774092
  • 财政年份:
    2014
  • 资助金额:
    $ 39.25万
  • 项目类别:
2012 Cornea, Biology & Pathobiology GRC
2012 角膜,生物学
  • 批准号:
    8250048
  • 财政年份:
    2012
  • 资助金额:
    $ 39.25万
  • 项目类别:
INTRACELLULAR LIFESTYLE OF PSEUDOMONAS AERUGINOSA
铜绿假单胞菌的细胞内生活方式
  • 批准号:
    7616052
  • 财政年份:
    2008
  • 资助金额:
    $ 39.25万
  • 项目类别:
INTRACELLULAR LIFESTYLE OF PSEUDOMONAS AERUGINOSA
铜绿假单胞菌的细胞内生活方式
  • 批准号:
    8391254
  • 财政年份:
    2008
  • 资助金额:
    $ 39.25万
  • 项目类别:
INTRACELLULAR LIFESTYLE OF PSEUDOMONAS AERUGINOSA
铜绿假单胞菌的细胞内生活方式
  • 批准号:
    7994835
  • 财政年份:
    2008
  • 资助金额:
    $ 39.25万
  • 项目类别:
INTRACELLULAR LIFESTYLE OF PSEUDOMONAS AERUGINOSA
铜绿假单胞菌的细胞内生活方式
  • 批准号:
    7743826
  • 财政年份:
    2008
  • 资助金额:
    $ 39.25万
  • 项目类别:

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