School of Optometry, University of California, Berkeley, CA, USA; Graduate Group in Vision Science, University of California, Berkeley, CA, USA; Graduate Groups in Microbiology and Infectious Diseases & Immunity, University of California, Berkeley, CA, USA.
School of Optometry, University of California, Berkeley, CA, USA.
Prog Retin Eye Res. 2020 May;76:100804. doi: 10.1016/j.preteyeres.2019.100804. Epub 2019 Nov 20.
Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can cause corneal infection (microbial keratitis), with an approximate annualized incidence ranging from ~2 to ~20 cases per 10,000 wearers, and sometimes resulting in permanent vision loss. Research suggests that the pathogenesis of contact lens-associated microbial keratitis is complex and multifactorial, likely requiring multiple conspiring factors that compromise the intrinsic resistance of a healthy cornea to infection. Here, we outline our perspective of the mechanisms by which contact lens wear sometimes renders the cornea susceptible to infection, focusing primarily on our own research efforts during the past three decades. This has included studies of host factors underlying the constitutive barrier function of the healthy cornea, its response to bacterial challenge when intrinsic resistance is not compromised, pathogen virulence mechanisms, and the effects of contact lens wear that alter the outcome of host-microbe interactions. For almost all of this work, we have utilized the bacterium Pseudomonas aeruginosa because it is the leading cause of lens-related microbial keratitis. While not yet common among corneal isolates, clinical isolates of P. aeruginosa have emerged that are resistant to virtually all currently available antibiotics, leading the United States CDC (Centers for Disease Control) to add P. aeruginosa to its list of most serious threats. Compounding this concern, the development of advanced contact lenses for biosensing and augmented reality, together with the escalating incidence of myopia, could portent an epidemic of vision-threatening corneal infections in the future. Thankfully, technological advances in genomics, proteomics, metabolomics and imaging combined with emerging models of contact lens-associated P. aeruginosa infection hold promise for solving the problem - and possibly life-threatening infections impacting other tissues.
隐形眼镜是一种广泛使用的视力矫正方式,全球有超过 1.4 亿人佩戴。尽管隐形眼镜通常被很好地耐受,但它也可能导致角膜感染(微生物性角膜炎),其年发病率约为每 10000 名佩戴者中有 2 至 20 例,有时会导致永久性视力丧失。研究表明,隐形眼镜相关微生物性角膜炎的发病机制复杂且多因素,可能需要多个协同因素来破坏健康角膜对感染的固有抵抗力。在这里,我们概述了我们对隐形眼镜佩戴有时使角膜易受感染的机制的看法,主要关注我们在过去三十年中的研究努力。这包括研究健康角膜固有屏障功能的宿主因素、当固有抵抗力不受损害时对细菌挑战的反应、病原体毒力机制,以及改变宿主-微生物相互作用结果的隐形眼镜佩戴的影响。对于几乎所有这些工作,我们都利用了铜绿假单胞菌,因为它是导致镜片相关微生物性角膜炎的主要原因。虽然在角膜分离株中尚未常见,但已经出现了对几乎所有现有抗生素都耐药的临床分离株铜绿假单胞菌,这导致美国疾病控制与预防中心(Centers for Disease Control)将铜绿假单胞菌添加到其最严重威胁的名单中。更令人担忧的是,用于生物传感和增强现实的先进隐形眼镜的发展,以及近视发病率的不断上升,可能预示着未来会出现威胁视力的角膜感染流行。值得庆幸的是,基因组学、蛋白质组学、代谢组学和成像技术的进步,以及新兴的隐形眼镜相关铜绿假单胞菌感染模型,为解决这一问题——以及可能危及生命的其他组织感染——带来了希望。