Biofilm development and Eye Infections

与隐形眼镜相关的眼部感染每年影响数百万人。标准的镜片护理指南可以将眼睛感染降至最低，但已有研究表明，只有约50%的镜片佩戴者遵守适当的指南。在通常的使用和储存过程中，微生物会附着在隐形眼镜上。日常的镜片清洁可以去除大部分这样的微生物，但有时微生物会在镜片上形成生物膜，尽管现有的消毒和清洁系统对这些生物膜进行了消毒和清洁，但这些生物膜往往没有得到令人满意的去除。在许多情况下，微生物的来源是透镜壳，在那里生物膜已经形成。 除了对晶状体消毒剂/清洁系统的耐药性外，病原菌形成的生物膜因其对抗生素的耐药性和宿主免疫反应以及在留置医疗设备上发展的能力而具有越来越重要的临床意义。一氧化氮(NO)已被证明通过产生NO的粒细胞的作用而有效地杀死哺乳动物宿主中的细菌和真菌。我们之前已经利用NO的抗微生物特性来创造出能够杀死浮游植物中的真菌和细菌的缓慢释放NO的化合物。在目前的调查中，我们将测试这种化合物也能够杀死在已建立的生物膜中生长的生物体的原理。在这种情况下，这项第一阶段提案的目的是检验没有任何治疗方法能够杀死的假设 由隐形眼镜相关眼部感染的病原体形成的生物膜的微生物细胞。将确定适当的细菌、真菌和混合生物膜对不处理的敏感性。 如果获得原则证据，在第二阶段进行的调查的最终目标是开发一种适当的镜片和镜盒灭菌的运送工具。我们将在第一阶段启动这项工作，这里也讨论了可能的方法。

Contact lens related eye infections impact millions of people yearly. Standard guidelines for lens care can minimize eye infection, but it has been shown that only about 50% of lens wearers adhere to appropriate guidelines. During usual use and storage procedures, microorganisms adhere to contact lenses. Daily lens cleaning removes most of these microorganisms, but sometimes microbes establish biofilms on lenses and often such biofilms are not satisfactorily removed despite disinfection and cleaning with systems currently available. In many cases the source of the microorganisms is the lens case where biofilms have developed. In addition to resistance to lens disinfectant/cleaning systems, biofilms formed by pathogenic organisms are of increasing clinical importance due to their resistance to antibiotics and host immune responses as well as their ability to develop on indwelling medical devices. Nitric oxide (NO) has been shown to efficiently kill bacteria and fungi in the mammalian host by the action of granulocytes that produce NO. We have previously exploited the antimicrobial properties of NO to create slow NO releasing compounds that are capable of killing both fungi and bacteria growing planktonically. In the present investigation, we will test the principle that such compounds are also capable of killing organisms growing in established biofilms. In this context, the aim of this Phase I proposal is to test the hypothesis that NO treatment is capable of killing microbial cells that comprise biofilms formed by causative agents of contact lens related eye infection. The sensitivity of appropriate bacterial, fungal, and mixed species biofilms to NO treatment will be determined. If proof of principle is obtained, the ultimate goal of the investigation to be pursued in Phase II is the development of an appropriate delivery vehicle for lens and lens case sterilization. We will initiate this work during Phase I, and possible approaches are also discussed herein.