title: Cytotoxicity of ganciclovir on cultured human corneal endothelial cells.
abstract: BACKGROUND
  Intraocular cytomegalovirus (CMV) infections, including endotheliitis and retinitis, have been reported to threaten the host's vision. These infections have been treated with systemic or intravitreal GCV injection. Intracameral GCV injection can be an effective treatment option that avoids systemic side effects. The cytotoxic effect of ganciclovir (GCV) on cultured human corneal endothelial cells (HCECs) was evaluated.
  
  
  METHODS
  HCECs were cultured and exposed to various concentrations (0-20 mg/ml) of GCV (Cytovene(®)). Cell viability was assessed by the Cell Counting Kit-8 method and live/dead viability/cytotoxicity assays. Cell morphology was assessed using phase-contrast microscopy after 48 h exposure to GCV. Cell cycle and apoptosis were analysed using NC-3000 to evaluate the effect of GCV on HCECs. The cell proliferation rate was evaluated by a bromodeoxyuridine proliferation assay.
  
  
  RESULTS
  Cytotoxicity tests showed that GCV had a dose-dependent cytotoxic effect on HCECs. GCV concentrations of ≥5 mg/ml resulted in a significant reduction in cell viability. Higher concentrations of GCV resulted in cell cycle delay, low proliferation rate, and an increased number of apoptotic cells, indicating activation of the pro-apoptotic pathway.
  
  
  CONCLUSIONS
  Our results suggest that intracameral GCV concentrations of ≥5 mg/ml may increase the risk of corneal endothelial damage, although GCV concentrations of ≤0.5 mg/ml do not decrease cell viability.
authors: Department of Ophthalmology, Hallym University College of Medicine, Seoul, Republic of Korea.
authors: Won Seok
authors: WS
authors: Choi
authors: Jae Woong
authors: JW
authors: Koh
authors: Tae Young
authors: TY
authors: Chung
authors: Joon Young
authors: JY
authors: Hyon
authors: Won Ryang
authors: WR
authors: Wee
authors: Young Joo
authors: YJ
authors: Shin
mesh_terms: D000998:Antiviral Agents / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004728:Endothelium, Corneal / Q000187:drug effects*; D015774:Ganciclovir / Q000633:toxicity*; D006801:Humans
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir