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D.T. Franc, J.R. Smith, N.S. Carter, D. Zamora, S.R. Planck, J.T. Rosenbaum; Preferential Susceptibility of Retinal Vascular Endothelium to Infection with Toxoplasma gondii Tachyzoites . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3242.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinochoroidal infection with the protozoan parasite, T. gondii, is the most common cause of posterior uveitis worldwide. Tachyzoites spread throughout the body via the blood stream, but preferentially encyst in the eye and other parts of the central nervous system. It is unclear whether T. gondii penetrates these areas preferentially or whether it is more difficult for such immunologically privileged sites to eradicate the organism. We hypothesize that preferential susceptibility of the retinal vascular endothelium to T.gondii tachyzoite infection contributes to the observed localization of the disease. Methods: Commercially available human vascular endothelial cell lines (Cascade Biologics and Applied Cell BioSystems), including retinal (3 lines from 3 different donors), dermal, aortic and umbilical vein endothelium, as well as human foreskin fibroblasts (HFF, the cell subtype generally used to investigate processes of T. gondii infection), were grown to confluence in 24-well plates. Cells were incubated at 37oC with RH-strain T. gondii tachyzoites (2x105/well) in MCDB-131 medium, supplemented with 5% fetal bovine serum and endothelial growth factors, for 2 hours, followed by a further 18 hours in the presence of [3H]-uracil (5 µCi/well). Trichloroacetic acid-insoluble radioactivity was measured as an index of T. gondii proliferation, because tachyzoites, but not human cells, take up and use uracil directly for pyrimidine salvage. Results: Tachyzoites showed significantly higher [3H]-uracil incorporation after incubation with retinal vascular endothelial cells in comparison with dermal (43% more, p = 0.047), aortic (56% more, p = 0.039) and human umbilical vein (33% more, p = 0.045) endothelial cells, by paired t-test. In contrast, an experiment comparing 3 different retinal endothelial lines revealed no significant difference between any pair (p > 0.300). Growth of the tachyzoites was approximately 2.6-fold higher in retinal endothelium than in HHF (p = 0.001). Interestingly, all tested vascular endothelial cell subtypes supported more tachyzoite growth than HFF (p < 0.05). Conclusions: Enhanced susceptibility of retinal vascular endothelium to infection by T. gondii tachyzoites may explain, at least in part, preferential localization of toxoplasmosis to the eye. Susceptibility may relate to preferential binding of tachyzoites to the retinal vascular endothelial surface, relative ease of penetration into the cell, rate of replication within the cell and/or cell survival.
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