title: Antiadenoviral effects of ganciclovir in types inducing keratoconjunctivitis by quantitative polymerase chain reaction methods.
abstract: OBJECTIVE
  The most common external ocular viral infections are caused by several human adenovirus (HAdV) types. Ganciclovir has been reported to inhibit cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, and Epstein-Barr virus. Ganciclovir ophthalmic gel, 0.15% (Virgan®) is commercially available for cytomegalovirus or herpes virus keratitis. However its inhibitory activity against HAdV is reported only for types 2 and 5. We investigated the antiadenoviral activity of ganciclovir in vitro in several common types currently inducing keratoconjunctivitis.
  
  
  METHODS
  A549 cells were used for viral cell culture, and adenovirus types 3 (HAdV3; species B), 4 (species E), and 8, 19a, and 37 (species D) were used. After pretreatment of A549 with serial dilutions of ganciclovir for 24 hours, adenovirus was cultured for 7 days, and adenoviral deoxyribonucleic acid was quantitatively measured by real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  The 50% cytotoxic concentration of ganciclovir was 212 μg/mL. The 50% effective concentration of ganciclovir obtained by real-time PCR ranged between 2.64 and 5.10 μg/mL. A significant inhibitory effect of ganciclovir on adenoviral proliferation was found in all types in a dose-dependent manner. The selectivity index of ganciclovir ranged between 41.6 and 80.3.
  
  
  CONCLUSIONS
  Ganciclovir showed significant inhibitory activity against HAdV3, 4, 8, 19a, and 37, which induce epidemic keratoconjunctivitis. These results indicate that ganciclovir is a possible candidate for the treatment of HAdV keratoconjunctivitis, and ganciclovir ophthalmic gel could be applied to adenoviral keratoconjunctivitis in the future.
authors: Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan.
authors: Jane
authors: J
authors: Huang
authors: Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan.
authors: Kazuaki
authors: K
authors: Kadonosono
authors: Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan.
authors: Eiichi
authors: E
authors: Uchio
keywords: A549 cell line; adenovirus; epidemic keratoconjunctivitis; ganciclovir; nucleoside analog