Intraocular caspofungin: in vitro safety profile for human ocular cells.
Endogenous Candida endophthalmitis is sight-threatening, difficult to treat and sometimes leads to loss of the eye. Only a few therapeutic agents are available for its treatment. Caspofungin is the first of a new class of antifungal drugs (echinocandins) with a high activity against Candida species, the most common pathogens found in endogenous endophthalmitis. This study investigates the safety profile of caspofungin for intraocular application in a cell-culture model. Endothelial toxicity of caspofungin was evaluated in cultured human corneas. Possible toxic effects of caspofungin (5-300 μg ml(-1)) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC) and primary human retinal pigment epithelium (RPE) cells were evaluated after 24 h and under conditions of inflammatory stress by treatment with tumour necrosis factor-alpha (TNF-α), lipopolysaccharides (LPS) or interleukin-6 (IL-6) and hydrogen peroxide (H(2)O(2)). Toxicity was evaluated by tetrazolium dye-reduction assay; cell viability was quantified by a microscopic live-dead assay. No corneal endothelial toxicity could be detected after 30 days of treatment with 75 μg ml(-1) of caspofungin. Concentrations up to 75 μg ml(-1) had no influence on CEC, TMC or RPE cell proliferation, or on cell viability when administered for 24 h. Exposure to H(2)O(2) did not increase cellular toxicity of caspofungin at concentrations of 5-50 μg ml(-1). After preincubation with TNF-α, LPS or IL-6 for 24 h followed by treatment with caspofungin for 24 h, no significant decrease in cell proliferation or viability was observed. This study showed no significant toxicity for caspofungin on CEC, TMC or RPE cells, or human corneal endothelium when administered in therapeutic concentrations up to 50 μg ml(-1).
Kernt
M
M
Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany. marcus.kernt@med.uni-muenchen.de
Kampik
A
A
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000633:toxicity*; D000077336:Caspofungin; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology; D054714:Echinocandins / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D055666:Lipopeptides; D008875:Middle Aged; D055213:Retinal Pigment Epithelium / Q000166:cytology; D013778:Tetrazolium Salts / Q000378:metabolism; D014129:Trabecular Meshwork / Q000166:cytology
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D013778:Tetrazolium Salts; D000077336:Caspofungin