Reproduction of antiviral effect in an in vivo model of human cytomegalovirus retinal infection.
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 beta-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 (identical to 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 beta-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 beta-galactosidase expression was found in any of 12 eyes from animals which had received ganciclovir treatment.


CONCLUSIONS
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.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
K A
KA
Laycock
Y
Y
Kumano
J S
JS
Pepose
D000818:Animals; D000867:Anterior Chamber / Q000601:surgery; D000998:Antiviral Agents / Q000008:administration & dosage*; D003587:Cytomegalovirus / Q000201:enzymology; D017726:Cytomegalovirus Retinitis / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage*; D006651:Histocytochemistry; D006801:Humans; D007274:Injections, Intraperitoneal; D051381:Rats; D011923:Rats, Nude; D012160:Retina / Q000187:drug effects / Q000637:transplantation / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*; D001616:beta-Galactosidase / Q000378:metabolism
D000998:Antiviral Agents; D001616:beta-Galactosidase; D015774:Ganciclovir