REPRODUCTION OF ANTIVIRAL EFFECT IN AN IN-VIVO MODEL OF HUMAN CYTOMEGALOVIRUS RETINAL INFECTION

Background: Cytomegalovirus retinitis remains a serious problem in AID S patients, and the species specificity of human cytomegalovirus (HCMV ) has hindered the development of animal models suitable for testing n ew 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 or der to determine the model's potential for evaluating novel agents. Me thods: Athymic rats had human fetal retinal tissue implanted in both a nterior chambers. At 14 or 28 days post implantation, a suspension of a beta-galactosidase (lacZ(+)) mutant of HCMV was injected into each a nterior chamber. Commencing 3 days prior to the injection of virus, ra ts in the treatment group received twice-daily intraperitoneal injecti ons of ganciclovir (= a total of 100 mg/kg per day) for the duration o f the study. The control rats received no drug. Twenty days after viru s injection, the eyes of all rats were removed, sectioned and develope d with X-gal substrate to detect any beta-galactosidase expression in the human tissue implants. Results: Blue-staining foci of infection we re detected in the implanted retinal tissue in 8 of 10 eyes from untre ated control rats, but no beta-galactosidase expression was found in a ny of 12 eyes from animals which had received ganciclovir treatment. C onclusion: Intraperitoneal administration of ganciclovir successfully prevented HCMV replication in the intraocular retinal implants. This m odel of HCMV retinal infection is therefore suitable for preliminary e valuation of systemically administered antiviral agents.