The mobile Acanthamoeba trophozoites can invade the cornea by several mechanisms, including adherence to corneal epithelium glycoproteins, release of cytolytic and/or apoptotic molecules and protease discharge in the corneal stroma. When trophozoites adhere to mannose glycoproteins on the corneal epithelium and subsequently produce a mannose-induced protein (MIP-133), that leads to corneal epithelial cytolisis. The amoebae can penetrate the epithelial basement membrane and Bowman’s membrane by releasing proteases and then infect the stromal keratocytes, potentially leading to corneal melting by the continuing action of proteases.
Clinical signs range from epithelial microerosion and patchy anterior stromal infiltrates, corneal ulcer, melting and dense corneal abscesses, in later phases of the disease. Typically, perineural involvement is characterized by severe ocular pain. Although Acanthamoeba sclerokeratitis is an immuno-mediated process, the amoebic infection rarely has been documented to spread beyond the cornea to affect the perilimbal and posterior ocular structures process (Dougherty PJ et al., 1994; Lee GA et al., 2002). Histopathologic evidence of A. culbertisoni cysts and trophozoites in the retina is available from 1 case report. Direct involvement of the posterior ocular structures without evidence of prior keratitis is rare and is believed to be the result of hematogenus spread, mainly in immuno-compromised patients.
A number of recent studies have progressed understanding of the molecular mechanism of AK reviewed by Panwari (2010). Work demonstrated Acanthamoebae expresses a major virulence protein, the mannose-binding protein (MBP) that mediates the adhesion of amoebae to the surface of the cornea. The MBP-mediated dynamic host-parasite interactions lead to the secretion of metallo- and serine-proteinases, which work in concert to produce potent cytopathic effect (CPE). Normal tear fluid contains highly potent protective factors against Acanthamoeba-induced CPE. These protective factors include both anti-MBP IgA that inhibits adhesion of amoebae to host cells, and IgA-independent factors that inhibit the activity of cytotoxic proteinases. Although future studies may characterise the CPE-inhibitory factors of human tears and could lead to a better understanding of the mechanism by which the tissues of the host resist the infection, the immediate need remains for effective biocide treatment.The focus of ODAK is the refinement and optimisation of an effective topical treatment for AK using PHMB.
Electron micrograph of an Acanthamoeba trophozoite excysting (left). The cyst wall is below the trophozoite which is extending its acanthapodia. (Middle) Acanthamoeba trophozoites migrating on non-nutrient agar overlain with E. coli (Right) Immunostain of Acanthamoeba within human corneal epithelium.