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In this review, the author summarised the current microbiomic and immunological evidence related to the pathogenesis of Acanthamoeba keratitis (AK). AK has been described for almost 50 years, but the exact biology of the disease remains perplexing. Acanthamoeba spp. are ubiquitous, with 90% to 100% of the population developing serum antibodies against Acanthamoeba antigens despite have never suffered from AK before. Contact-lens wear is the leading risk factor, though the incidence is very low even amongst the 30 million contact-lens users in the US. AK leads to relentless damage to the corneal epithelium, stromal melt, and clinically it is frequently confused with herpetic keratitis. The associated radial keratoneuritis is associated with extreme pain compared to the degree of clinical signs. The pathogenesis of AK starts with trophozoites binding to mannosylated proteins on corneal epithelium, which are upregulated after abrasions or contact-lens wear. The trophozoites subsequently release mannose-induced protease 133, which leads to stromal melting by degradation of stromal matrix. Constituents of ocular microbiome could influence the pathogenesis of AK. Presence of Corynebacterium xerosis exacerbates AK by facilitating trophozoite invasion of the stromal and corneal cytolysis. Macrophages and neutrophils, part of the innate immune system, are able to kill both Acanthamoeba cysts and trophozoites in vitro. Acanthamoeba antigens are able to mount robust adaptive immune response, though IgG fails to mitigate nor prevent AK. As many patients suffering from AK require corneal transplant and corticosteroids are routinely used to prevent corneal graft rejection, this is especially problematic and reinfection is always a threat. On the other hand, secretory IgA antibodies in the tear are able to block the initial adhesion Acanthamoeba trophozoites to the corneal epithelium. Though once the trophozoites penetrate the ocular surface, IgA antibodies can no longer mediate AK.

The biology of Acanthamoeba keratitis.
Niederkorn J.
2020;Epub ahead of print.
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Siyin Liu

Manchester Royal Eye Hospital, UK.

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