Experimental ocular toxoplasmosis induced in naive and preinfected mice by intracameral inoculation.
We have developed a murine model to investigate the pathogenesis of acquired ocular toxoplasmosis. Tachyzoites of PLK strain of Toxoplasma gondii were intracamerally inoculated under anesthesia into the right eyes of naive or perorally preinfected C57BL/6 and MRL-MpJ mice. Clinical and histopathological observations of responses to intraocular infection were analyzed. Ocular inflammation from Toxoplasma gondii is dose-dependent in both strains of mice. After inoculation of fifty parasites, no evidence of inflammation was observed in the eyes of naive mice. The eyes of naive mice that received 500 or 5,000 parasites developed inflammatory changes by day 6 post challenge. By day 8, the changes progressed to moderate to severe intraocular inflammation. Histologic analysis of the ocular lesions demonstrated mononuclear cell infiltration and necrosis predominantly in the anterior segment of the eyes of the naive mice. Inoculation of 50,000 tachyzoites induced a destructive ocular inflammatory response and was uniformly lethal to the mice by approximately one week after challenge. In contrast, eyes from mice previously orally infected with Toxoplasma gondii and that received a 50 or 500 parasite intracameral challenge revealed no inflammation, but the eyes receiving 5,000 parasites demonstrated necrotic focal retinochoroiditis with vitreitis by day 8 after challenge. The murine model reproduces some features of ocular toxoplasmosis in humans and may be suitable for large-scale controlled studies of the pathogenesis and therapeutics of acquired ocular toxoplasmosis as well as for study of the mechanisms of immune privilege in the eye.
Department of Medicine, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. Mark.S.Hu@Dartmouth.EDU
M S
MS
Hu
J D
JD
Schwartzman
A C
AC
Lepage
I A
IA
Khan
L H
LH
Kasper
D000818:Animals; D000867:Anterior Chamber / Q000469:parasitology*; D002825:Chorioretinitis / Q000469:parasitology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D019463:Mice, Inbred MRL lpr; D014122:Toxoplasma / Q000472:pathogenicity*; D014126:Toxoplasmosis, Ocular / Q000469:parasitology* / Q000473:pathology