Abstract
Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. Staphylococcus aureus and Pseudomonas aeruginosa are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. In vitro, ex vivo and in vivo corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface.
Highlights
Bacterial keratitis is a potentially sight-threatening eye infection, localised to the cornea.The infection is characterised by the presence of replicating bacteria on the ocular surface, which disrupt the integrity of the corneal epithelium and result in inflammation of the corneal stroma [1].Early symptoms include pain, redness, excessive lacrimation, light sensitivity and blurred vision.Examination of the eye reveals lid oedema, congestion of conjunctiva, corneal haze and a variableCells 2020, 9, 2450; doi:10.3390/cells9112450 www.mdpi.com/journal/cellsCells 2020, 9, 2450 degree of inflammation of the anterior chamber
Knockdown of MUC16 in the HCLE cell line causes significant decreases in epithelial barrier function [128] and exposure of primary rabbit corneal epithelial cells to human tear fluid has been shown to confer significant cytoprotective effects, as well as reducing the translocation of P. aeruginosa [129,130]. These in vitro infection models have helped to progress our understanding of bacterial keratitis, but they are limited by the absence of a biofilm component
In agreement with Pinnock et al, we recently demonstrated that there was no significant difference in viable cell count between ex vivo porcine and rabbit cornea models after 24 h infection, nor when two different strains of P. aeruginosa were used [151]
Summary
Bacterial keratitis is a potentially sight-threatening eye infection, localised to the cornea. Reported risk factors include corneal trauma, contact lens-wear, chronic ocular surface disease, ocular surgery and systemic diseases associated with an immunocompromised state [10,11] These factors compromise the resistance mechanisms employed by the cornea, rendering it newly susceptible to infection [9]. Corneal trauma constitutes the major risk factor in the development of microbial keratitis and this is thought to reflect the increased size of the agricultural workforce in these countries, e.g., rice stalks and thorns are a common cause of ocular injury for farmers in South India [13,14] Support for this is provided by a recent epidemiological study, conducted in. In Minnesota, a 435% increase in microbial keratitis was recorded over a 39-year period, following the introduction of contact-lenses [17]
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