Reproduction of antiviral effect in an in vivo model of human cytomegalovirus retinal infection

Abstract 

· Background: Cytomegalovirus retinitis remains a serious problem in AIDS patients, and the species specificity of human cytomegalovirus (HCMV) has hindered the development of animal models suitable for testing new therapeutic agents. Having previously described an in vivo model of HCMV retinal infection, we investigated its ability to reproduce the antiviral effects of the established anti-HCMV agent ganciclovir in order to determine the model’s potential for evaluating novel agents. · Methods: Athymic rats had human fetal retinal tissue implanted in both anterior chambers. At 14 or 28 days post implantation, a suspension of a β-galactosidase (lacZ⁺) mutant of HCMV was injected into each anterior chamber. Commencing 3 days prior to the injection of virus, rats in the treatment group received twice-daily intraperitoneal injections of ganciclovir (≡ a total of 100 mg/kg per day) for the duration of the study. The control rats received no drug. Twenty days after virus injection, the eyes of all rats were removed, sectioned and developed with X-gal substrate to detect any β-galactosidase expression in the human tissue implants. · Results: Blue-staining foci of infection were detected in the implanted retinal tissue in 8 of 10 eyes from untreated control rats, but no β-galactosidase expression was found in any of 12 eyes from animals which had received ganciclovir treatment. · Conclusion: Intraperitoneal administration of ganciclovir successfully prevented HCMV replication in the intraocular retinal implants. This model of HCMV retinal infection is therefore suitable for preliminary evaluation of systemically administered antiviral agents.