PURPOSE: Topical steroids are frequently used to control corneal inflammation and uveitis or is administered after surgery, to prevent corneal graft rejection. This study was undertaken to determine whether steroids could affect the pathogenicity of Acanthamoeba castellanii. METHODS: The effect of dexamethasone phosphate on excystment, proliferation, and encystment of trophozoites and cysts of A. castellanii was examined in vitro. Cytolysis capacity of steroid-treated Acanthamoeba was quantified by a spectrophotometric assay, and plasminogen activators were measured by a fibrinolysis assay. The influence of steroid treatment on corneal infection in a Chinese hamster model of Acanthamoeba keratitis was examined in vivo. RESULTS: Treatment of Acanthamoeba cysts with dexamethasone induced 4- to 10-fold increases in the number of trophozoites compared with untreated control cultures. Acceleration of trophozoite proliferation was observed when trophozoites were treated with dexamethasone. However, dexamethasone treatment did not affect encystment of Acanthamoeba trophozoites. Dexamethasone-treated trophozoites or cysts induced a significant cytopathic effect on corneal epithelial cells compared with untreated organisms. Supernatants collected from either dexamethasone-treated or untreated organisms failed to lyse corneal epithelial cells. Treatment of organisms with dexamethasone had no effect on production of plasminogen activators by Acanthamoeba trophozoites. Intramuscular injection of dexamethasone had a profound effect on the incidence, severity, and chronicity of keratitis. Keratitis in dexamethasone-treated hamsters was significantly more severe at all time points than in untreated animals (P < 0.05). CONCLUSIONS: These findings indicate that exposure of Acanthamoeba trophozoites and cysts to dexamethasone increases the pathogenicity of the organisms. The results emphasize the importance of maintaining adequate amebicidal therapy if a topical steroid is used in the management of Acanthamoeba keratitis.
PURPOSE: Topical steroids are frequently used to control corneal inflammation and uveitis or is administered after surgery, to prevent corneal graft rejection. This study was undertaken to determine whether steroids could affect the pathogenicity of Acanthamoeba castellanii. METHODS: The effect of dexamethasone phosphate on excystment, proliferation, and encystment of trophozoites and cysts of A. castellanii was examined in vitro. Cytolysis capacity of steroid-treated Acanthamoeba was quantified by a spectrophotometric assay, and plasminogen activators were measured by a fibrinolysis assay. The influence of steroid treatment on corneal infection in a Chinese hamster model of Acanthamoeba keratitis was examined in vivo. RESULTS: Treatment of Acanthamoeba cysts with dexamethasone induced 4- to 10-fold increases in the number of trophozoites compared with untreated control cultures. Acceleration of trophozoite proliferation was observed when trophozoites were treated with dexamethasone. However, dexamethasone treatment did not affect encystment of Acanthamoeba trophozoites. Dexamethasone-treated trophozoites or cysts induced a significant cytopathic effect on corneal epithelial cells compared with untreated organisms. Supernatants collected from either dexamethasone-treated or untreated organisms failed to lyse corneal epithelial cells. Treatment of organisms with dexamethasone had no effect on production of plasminogen activators by Acanthamoeba trophozoites. Intramuscular injection of dexamethasone had a profound effect on the incidence, severity, and chronicity of keratitis. Keratitis in dexamethasone-treated hamsters was significantly more severe at all time points than in untreated animals (P < 0.05). CONCLUSIONS: These findings indicate that exposure of Acanthamoeba trophozoites and cysts to dexamethasone increases the pathogenicity of the organisms. The results emphasize the importance of maintaining adequate amebicidal therapy if a topical steroid is used in the management of Acanthamoeba keratitis.
Authors: C E Oldenburg; J D Keenan; V Cevallos; M F Chan; N R Acharya; B D Gaynor; S D McLeod; E J Esterberg; T C Porco; T M Lietman Journal: Eye (Lond) Date: 2011-06-03 Impact factor: 3.775