Human Retinal Organoid Model of Ocular Toxoplasmosis
Files
(Published version)
Date
2025
Authors
Ashander, L.M.
Lidgerwood, G.E.
Lumsden, A.L.
Furtado, J.M.
Pébay, A.
Smith, J.R.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Pathogens, 2025; 14(3):286-1-286-17
Statement of Responsibility
Liam M. Ashander, Grace E. Lidgerwood, Amanda L. Lumsden, João M. Furtado, Alice Pébay, and Justine R. Smith
Conference Name
Abstract
The health burden of ocular toxoplasmosis is substantial, and there is an unmet need for safe and curative anti-microbial drugs. One major barrier to research on new therapeutics is the lack of in vitro human-based models beyond two-dimensional cultured cells and tissue explants. We aimed to address this research gap by establishing a human retinal organoid model of ocular toxoplasmosis. Retinal organoids, generated from human induced pluripotent stem cells and grown to two stages of organization, were incubated with a suspension of live or heat-killed GT-1 strain T. gondii tachyzoites, or medium without tachyzoites. Both developing (1 month post-isolation) and matured (6 months post-isolation) organoids were susceptible to infection. Spread of live parasites from the margin to the entire organoid over 1 week was indicated by immunolabelling for T. gondii surface antigen 1. This progression was accompanied by changes in the levels of selected tachyzoite transcripts—SAG1, GRA6, and ROP16—and human cytokine transcripts—CCL2, CXCL8, CXCL10, and IL6—in infected versus control conditions. Our human retinal organoid model of ocular toxoplasmosis offers the opportunity for many future lines of study, including tachyzoite interactions with retinal cell populations and leukocyte subsets, parasite stage progression, and disease processes of different T. gondii strains, as well as drug testing.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).