June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Role of TgWIP on the migration of Toxoplasma gondii into the eye
Author Affiliations & Notes
  • Vanessa Rozo
    Department of Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
  • Sangwan Park
    Department of Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
  • Lamba O Sangare
    Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • David Arranz Solis
    Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Sara M Thomasy
    Department of Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
    Department of Ophthalmology & Vision Science, University of California Davis, Davis, California, United States
  • Jeroen Saeij
    Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Brian C Leonard
    Department of Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Vanessa Rozo None; Sangwan Park None; Lamba Sangare None; David Solis None; Sara Thomasy None; Jeroen Saeij None; Brian Leonard None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1681 – A0511. doi:
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    • Get Citation

      Vanessa Rozo, Sangwan Park, Lamba O Sangare, David Arranz Solis, Sara M Thomasy, Jeroen Saeij, Brian C Leonard; Role of TgWIP on the migration of Toxoplasma gondii into the eye. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1681 – A0511.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Ocular involvement occurs in about 70-90% of patients infected with Toxoplasma gondii. The genetic determinants of T. gondii that allow the parasite to migrate across the blood-retinal-barrier are poorly understood. Identification of genetic factors are critical to understanding the pathogenesis of T. gondii and may provide novel strategies for therapeutic intervention. A previous large-scale screen identified the parasite secreted effector TgWIP as a potential candidate gene that influences parasitic migration to the eye. Upon invasion, T. gondii secretes TgWIP into the host cytosol and enhances dendritic cell motility and transmigration, potentially turning them into shuttling vectors of T. gondii to the eye.

Methods : CRISPR-Cas9 was used to generate T. gondii parasites lacking TgWIP (△TgWIP). CD-1 mice were infected with 200,000 parasites/mouse in 4 groups: wildtype (WT) intravenously (IV) (n=5), WT intraperitoneally (IP) (n=5), △TgWIP IV (n=5), △TgWIP IP (n=5). Mice were sedated, examined, and imaged at baseline and at 7 days post-infection (pi) using slit-lamp biomicroscopy, indirect fundoscopy, posterior segment optical coherence tomography (OCT), color fundus photography, and fluorescein angiography (FA). Animals were euthanized on day 7, globes were fixed and processed for histologic analysis and immunohistochemistry for identification of parasites.

Results : All animals survived to day 7 pi, however one mouse died from the WT IV group during imaging. Fundic photography demonstrated marked vasodilation pi in all treatment groups with △TgWIP IV infected mice having the greatest degree of retinal vessel dilation from baseline to day 7, followed by △TgWIP IP, WT IV, and WT IP. FA revealed poorly delineated vasculature at day 7 compared to baseline, indicative of increased vascular permeability. Moderate thickening of the choroid was evident on OCT at day 7 pi with △TgWIP infected animals demonstrating a significantly more pronounced thickening when compared with WT infected controls. Histopathologic analysis and immunolocalization of T. gondii are currently being performed.

Conclusions : All mice infected with T. gondii demonstrated vascular dilation and increased vascular permeability with a subjectively more significant effect in animals infected with △TgWIP irrespective of infection route. The role of TgWIP in parasite migration and inflammatory changes to the eye requires further investigation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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