Contact Lens Wear, Bacteria, and Corneal Homeostasis

摘要： 仅在美国就有4000万人戴隐形眼镜，隐形眼镜与视力威胁有关 感染。随着近视预防的使用越来越多，以及为技术目的开发镜片的努力，一种 预计镜片使用量将激增(特别是延长佩戴时间)。不幸的是，与镜片相关的研究 由于缺乏适用于现有许多研究工具的体内模型，并发症一直受到阻碍 只有老鼠才能吃。经过25年的努力，我们已经开发出了一款鼠标隐形眼镜佩戴模型。这利用了 硅胶水凝胶隐形眼镜由隐形眼镜制造商定制，适合老鼠眼睛，不需要盖子 缝合。当被最常见的铜绿假单胞菌污染时，镜片会导致角膜感染。 人类隐形眼镜相关性角膜炎的病原体。 了解隐形眼镜相关感染的基础是了解在没有隐形眼镜的情况下隐形眼镜如何影响角膜 细菌接种。初步数据显示，老鼠模型复制了在实验期间发生的多个事件 人类晶状体磨损，包括晶状体与共生型细菌和树突状细胞(DC)的定植 24小时内响应。超出人类受试者的可行范围，高分辨率延时 对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 穿戴6天后，中性粒细胞在基质中。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 处于组织动态平衡和经典炎症反应中间状态的低度炎症反应 持续组织应激…可引起的炎症 这个项目的三个目标将探索：1)配戴隐形眼镜时副炎症的触发因素，2)如何 信号在角膜内传导以驱动Ly6G+细胞反应，以及3)其在微生物中的意义 挑战。根据已发表的初步数据，该假说是接触过程中的副火焰 小鼠戴晶状体的原因可能是细菌侵袭晶状体，引发一系列事件，而不是其他原因。 发生在正常的无微生物的角膜中，这种角膜具有保护其免受共生型细菌的作用， 但这会刺激角膜对铜绿假单胞菌做出过度侵略性的反应。 好了！

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. !