Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

Abstract

Until recently, the ocular surface is thought by many to be sterile and devoid of living microbes. It is now becoming clear that this may not be the case. Recent and sophisticated PCR analyses have shown that microbial DNA-based “signatures” are present within various ethnic, geographic, and contact lens wearing communities. Furthermore, using a mouse model of ocular surface disease, we have shown that the microbe, Corynebacterium mastitidis (C. mast), can stably colonize the ocular mucosa and that a causal relationship exists between ocular C. mast colonization and beneficial local immunity. While this constitutes proof-of-concept that a bona fide ocular microbiome that tunes immunity can exist at the ocular surface, there remain numerous unanswered questions to be addressed before microbiome-modulating therapies may be successfully developed. Here, the authors will briefly outline what is currently known about the local ocular microbiome as well as microbiomes associated with other sites, and how those sites may play a role in ocular surface immunity. Understanding how commensal microbes affect the ocular surface immune homeostasis has the potential revolutionize how we think about treating ocular surface disease.

Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data

“…The large fall out of articles was partly due to a high yield of research on the flower iris (publications n = 549) and publications on veterinarian topics (publications n = 859). Based on the inclusion criteria, 76 articles were included: 35 reported on original research (27 on human ocular surface amplicon sequencing, 5 on murine ocular surface amplicon sequencing (Terzulli et al 2015; de Paiva et al 2016; Kugadas et al 2016; St. Leger et al 2017; Wan et al 2018), 1 on intra‐ocular amplicon sequencing and 2 publications using shotgun sequencing), 14 reviews (Willcox 2013; Zegans & Van Gelder 2014; Kugadas & Gadjeva 2016; Lu & Liu 2016; Boost et al 2017; St. Leger & Caspi 2018; Wen et al 2018; Baim et al 2019; Borroni et al 2019; Gallon et al 2019; Watane et al 2019; Cavuoto et al, 2019a, 2019b, 2019c; Ozkan & Willcox 2019) and 27 abstracts (summarized in Table ). When taking into account only amplicon sequencing research on human ocular surface, there is an evident increase in original publications since 2016 (Fig.…”

NLRP3, NLRP12, and IFI16 Inflammasomes Induction and Caspase-1 Activation Triggered by Virulent HSV-1 Strains Are Associated With Severe Corneal Inflammatory Herpetic Disease

“…The inflammasome-virulence-gene associations and their impacts on viral fitness, inflammasome activation, inflammatory responses and virulence will be subject of a future report. Finally, it is not excluded that ocular surface microbiome and the wide range of ocular microbial DNA-based “signatures” recently reviewed by St. Leger et al (87), also affect the level and type of inflammasomes activated following ocular infection with the virulent and less virulent strains of HSV-1. There are several implications of the finding that the level of expression of NLRP3, NLRP12, and IFI16 inflammasomes is increase following infection virulent HSV-1 strains and this was associated with severe corneal inflammatory herpetic disease.…”

Current Evidence for Corynebacterium on the Ocular Surface

“…C. mastitidis was first found in sheep with mastitis [ 50 ] and this species can stably colonize the ocular mucosa, where it provides a related beneficial local immunity [ 51 ]. Bernard and associates analyzed C. mastitidis recognized by Eguchi in Japan and Vandamm in Belgium and Switzerland [ 8 , 52 ], and described C. lowii and C. oculi as two new species, separate from C. mastitidis .…”