IFN-gamma-regulated Toxoplasma gondii distribution and load in the murine eye.

Purpose: To establish a mouse model of ocular toxoplasmosis in both wild type (WT) and immunocompromised hosts and to clarify the effects of interferon (IFN)-gamma on the infectivity of Toxoplasma gondii in various parts of the eye.

Methods: Susceptible WT C57BL/6, resistant WT BALB/c, and IFN-gamma knockout (GKO) mice were infected with cysts of T. gondii perorally. The tissues were harvested for molecular and histopathologic studies. Analysis included a quantitative competitive polymerase chain reaction (QC-PCR) assay and reverse transcription (RT)-PCR for IFN-gamma and stage conversion markers. All animals underwent ophthalmic examinations including fluorescein angiography (FA).

Results: In WT C57BL/6 mice, T. gondii was detected in tissue in the following order: brain, retina, choroid, sclera, and optic nerve (ON). The highest T. gondii load was observed in the posterior retina, and was much greater than that in WT BALB/c mice. In GKO mice, disseminated infection was evident, and the T. gondii load was highest in the choroid and ON. IFN-gamma mRNA expression in WT C57BL/6 mice was higher than that in WT BALB/c mice after infection. Tachyzoites existed in GKO mice, whereas bradyzoites existed in WT C57BL/6 mice. FA showed dye leakage from the retinal capillaries of GKO mice.

Conclusions: The T. gondii load in the retina in the susceptible WT strain continued to increase, unlike in the resistant WT strain. IFN-gamma was shown to regulate the T. gondii load and interconversion in the eye. A toxoplasmic vasculitis model was established with GKO mice and assay systems with QC-PCR and FA.