Pathogenesis of Acanthamoeba Keratitis

Abstract

Acanthamoeba keratitis (AK) is a serious infection of the cornea. At present, diagnosis of the disease is not straightforward and treatment is very demanding. While contact lens wear is the leading risk factor for AK, Acanthamoeba parasites are increasingly recognized as an important cause of keratitis in non-contact lens wearers. The first critical step in the pathogenesis of infection is the adhesion of the microbe to the surface of the host tissues. Acanthamoebae express a major virulence protein, the mannose-binding protein (MBP), which mediates the adhesion of amoebae to the surface of the cornea. The MBP is a transmembrane protein with characteristics of a typical cell surface receptor. Subsequent to the MBP-mediated adhesion to host cells, the amoebae produce a contact-dependent metalloproteinase and several contact-independent serine proteinases. These proteinases work in concert to produce a potent cytopathic effect (CPE) involving killing of the host cells, degradation of epithelial basement membrane and underlying stromal matrix, and penetration into the deeper layers of the cornea. In the hamster animal model, oral immunization with the recombinant MBP protects against AK, and this protection is associated with an increased level of anti-MBP IgA in tears of protected animals. Normal human tear fluid contains IgA antibodies against Acanthamoeba MBP that is likely to provide protection by inhibiting the adhesion of parasites to host cells. Indeed, in in vitro CPE assays, even a low concentration of tears (10 [MU]μL of undiluted tears per milliliter of media) almost completely inhibits Acanthamoeba-induced CPE. In addition to adherence-inhibiting, IgA-mediated protection, human tears also contain IgA-independent factors that provide protection against Acanthamoeba-induced CPE by inhibiting the activity of cytotoxic proteinases. Characterization of the CPE-inhibitory factors of human tears should lead to a better understanding of the mechanism by which the tissues of the host resist the infection and also help decode circumstances that predispose to Acanthamoeba infections.

Pathological characteristics of the different stages of Acanthamoeba keratitis

“…Acanthamoeba propagates by forming cysts. Cyst adhesion to the corneal epithelium is a primary step in Acanthamoeba keratitis . In this study, pathomorphological observations of the development stage showed that the corneal epithelia were defective in the lesion area, and a uniform membrane, stained pink by PAS, was seen at the site of the defective epithelium.…”

Pathological characteristics of the different stages of Acanthamoeba keratitis

“…Acanthamoeba propagates by forming cysts. Cyst adhesion to the corneal epithelium is a primary step in Acanthamoeba keratitis . In this study, pathomorphological observations of the development stage showed that the corneal epithelia were defective in the lesion area, and a uniform membrane, stained pink by PAS, was seen at the site of the defective epithelium.…”

Tannic Acid-Modified Silver Nanoparticles in Conjunction with Contact Lens Solutions Are Useful for Progress against the Adhesion of Acanthamoeba spp. to Contact Lenses

“…The adhesion of Acanthamoeba trophozoites to contact lenses and their transmission from the contact lens surface to the corneal epithelium is the first step to AK development [11]. Here, we showed that adhesion to lenses composed of ionized material (FDA groups 3 and 4) was much higher and stronger compared to non-ionized lenses (FDA groups 1 and 2) [27].…”

Acanthamoeba keratitis – Clinical signs, differential diagnosis and treatment

“…In case of a corneal infection, as a first step, acanthamoeba are attached to the corneal epithelial cells through the Mannose-binding Protein. This binding supports secretion of metalloproteinase, serin- and cysteine proteinase through acanthamoeba, which results in cytotoxic effects on human corneal epithelial cells and keratocytes and supports deeper corneal penetration of acanthamoeba 11, 12, 13…”

Pathological characteristics of the different stages of Acanthamoeba keratitis

“…Acanthamoeba propagates by forming cysts. Cyst adhesion to the corneal epithelium is a primary step in Acanthamoeba keratitis . In this study, pathomorphological observations of the development stage showed that the corneal epithelia were defective in the lesion area, and a uniform membrane, stained pink by PAS, was seen at the site of the defective epithelium.…”

Tannic Acid-Modified Silver Nanoparticles in Conjunction with Contact Lens Solutions Are Useful for Progress against the Adhesion of Acanthamoeba spp. to Contact Lenses

“…The adhesion of Acanthamoeba trophozoites to contact lenses and their transmission from the contact lens surface to the corneal epithelium is the first step to AK development [11]. Here, we showed that adhesion to lenses composed of ionized material (FDA groups 3 and 4) was much higher and stronger compared to non-ionized lenses (FDA groups 1 and 2) [27].…”

Acanthamoeba keratitis – Clinical signs, differential diagnosis and treatment

“…In case of a corneal infection, as a first step, acanthamoeba are attached to the corneal epithelial cells through the Mannose-binding Protein. This binding supports secretion of metalloproteinase, serin- and cysteine proteinase through acanthamoeba, which results in cytotoxic effects on human corneal epithelial cells and keratocytes and supports deeper corneal penetration of acanthamoeba 11, 12, 13…”

Pathological characteristics of the different stages of Acanthamoeba keratitis

“…Acanthamoeba propagates by forming cysts. Cyst adhesion to the corneal epithelium is a primary step in Acanthamoeba keratitis . In this study, pathomorphological observations of the development stage showed that the corneal epithelia were defective in the lesion area, and a uniform membrane, stained pink by PAS, was seen at the site of the defective epithelium.…”

Tannic Acid-Modified Silver Nanoparticles in Conjunction with Contact Lens Solutions Are Useful for Progress against the Adhesion of Acanthamoeba spp. to Contact Lenses

“…The adhesion of Acanthamoeba trophozoites to contact lenses and their transmission from the contact lens surface to the corneal epithelium is the first step to AK development [11]. Here, we showed that adhesion to lenses composed of ionized material (FDA groups 3 and 4) was much higher and stronger compared to non-ionized lenses (FDA groups 1 and 2) [27].…”

Acanthamoeba keratitis – Clinical signs, differential diagnosis and treatment

“…In case of a corneal infection, as a first step, acanthamoeba are attached to the corneal epithelial cells through the Mannose-binding Protein. This binding supports secretion of metalloproteinase, serin- and cysteine proteinase through acanthamoeba, which results in cytotoxic effects on human corneal epithelial cells and keratocytes and supports deeper corneal penetration of acanthamoeba 11, 12, 13…”