Ka. Laycock et al., REPRODUCTION OF ANTIVIRAL EFFECT IN AN IN-VIVO MODEL OF HUMAN CYTOMEGALOVIRUS RETINAL INFECTION, Graefe's archive for clinical and experimental ophthalmology, 236(7), 1998, pp. 527-530
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.