Intracameral voriconazole: in vitro safety for human ocular cells.
Fungal keratitis is a sight-threatening infection of the cornea. It sometimes leads to loss of the eye. Despite an expanding range of fungal pathogens, there are only few therapeutic agents for its treatment available. Voriconazole is a second-generation synthetic triazole with a broad action against yeasts and molds. The current study investigates the safety of voriconazole for intracameral application in a cell culture model. Endothelial toxicity of voriconazole was evaluated in cultured human corneas. Possible toxic effects of voriconazole (10 microg /mL-10mg/mL) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC), and primary human retinal pigment epithelium (RPE) cells were evaluated after 24h and under conditions of inflammatory stress by treatment with tumor-necrosis-factor alpha (TNF-alpha), lipopolysaccharides (LPS), or interleukin-6 (IL-6) and hydrogen peroxide. Toxicity was evaluated by tetrazolium dye-reduction assay, and cell viability was quantified by a microscopic live-dead assay. No corneal endothelial toxicity could be detected after 30 days of treatment with 250 microg /mL of voriconazole. Concentrations up to 1mg/mL had no influence on CEC, TMC, or RPE cell proliferation, or on cell viability when administered for 24h. Hydrogen peroxide exposure did not increase cellular toxicity of voriconazole at concentrations from 10 to 250 microg /mL. After preincubation with TNF-alpha, LPS, or IL-6 for 24h and subsequent voriconazole treatment for 24h, no significant decrease in proliferation or viability was observed. This study showed no significant toxicity for voriconazole on CEC, TMC, RPE cells, or human corneal endothelium when administered in therapeutic concentrations up to 250 microg /mL.
Kernt
M
M
Department of Ophthalmology, Ludwig-Maximilians-University, Mathilden St. 8, 80336 Munich, Germany. marucs.kernt@med.uni-muenchen.de
Kampik
A
A
D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects; D005123:Eye / Q000166:cytology* / Q000187:drug effects*; D005562:Formazans / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D015394:Molecular Structure; D009924:Organ Culture Techniques; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects; D011743:Pyrimidines / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects; D014230:Triazoles / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D065819:Voriconazole
D000935:Antifungal Agents; D016895:Culture Media, Serum-Free; D005562:Formazans; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011743:Pyrimidines; D013778:Tetrazolium Salts; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C079782:MTT formazan; D006861:Hydrogen Peroxide; D065819:Voriconazole