The biology of Acanthamoeba keratitis

Abstract

Acanthamoeba keratitis (AK) is a rare protozoal infection of the cornea. At least eight species of Acanthamoeba are known to cause this sight-threatening disease of the ocular surface. Acanthamoeba spp. exist in a wide array of niches ranging from thermal springs to under ice and every conceivable habitat in between. Contact lens wear is the leading risk factor for AK and is practiced by over 30 million individuals in the United States, yet the incidence of AK is less than 33 cases per one million contact lens wearers. Serological studies have reported that 90%-100% of individuals with no history of AK possess antibodies specific for Acanthamoeba antigens indicating that exposure to this organism is commonplace, yet disease is remarkably rare. Animal studies have shed light on the pathobiology and immunobiology of AK and indicate that a constellation of factors including the ocular surface microbiome and the microbiome of Acanthamoeba itself contribute to the pathogenesis of AK. Interesting, secretory antibodies produced by the adaptive immune response can prevent the initiation of corneal infection, but once Acanthamoeba trophozoites breach the corneal epithelium the adaptive immune system is helpless in altering the course of AK. It has been almost 50 years since AK was first described, yet many questions remain unanswered about this curious and enigmatic disease of the ocular surface.

Keywords: Acanthamoeba; Contact lens; Cornea; Immunology; Keratitis; Microbiome; Pathology.

Figure 1.

Clinical appearance of Acanthamoeba keratitis. A. Ring-like infiltrate of the cornea that is a characteristic clinical lesion in Acanthamoeba infections of the cornea. B. Radial keratoneuritis (arrows) is associated with trophozoites juxtaposed to corneal nerves. Images courtesy of James P. McCulley, M.D. and reproduced with permission (Clarke and Niederkorn, 2006).

Figure 2.

Schematic depiction of the pathophysiology of Acanthamoeba keratitis. 1. Trophozoites bind to mannosylated proteins that are upregulated in response to corneal abrasions or contact lens wear. 2. Engagement of mannosylated proteins with the mannose-binding receptor on trophozoites stimulates trophozoites to release mannose-induced protease 133 (MIP-133), which lyses corneal cells. 3. MIP-133 facilitates trophozoite penetration of Bowman’s membrane. 4. MIP-133 leads to “stromal melting” by degradation of the collagenous stromal matrix. 5. Trophozoites accumulate around corneal nerves and are associated with radial keratoneuritis and exquisite pain. 6. Trophozoites almost never progress to the posterior regions of the eye. Reproduced with permission (Clarke and Niederkorn, 2006).