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Updated: Jun 25, 2026
Toxicity Screens in Human Retinal Organoids for Pharmaceutical Discovery
Published on: March 4, 2021
Human Retinal Organoid Model of Ocular Toxoplasmosis
Liam M Ashander1, Grace E Lidgerwood2, Amanda L Lumsden1
1Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia.
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.
Insights
Researchers developed a human retinal organoid model to study ocular toxoplasmosis. This model effectively mimics parasite infection and host responses, paving the way for new drug development for this serious eye disease.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Stem Cell Biology
- Parasitology
Background:
- Ocular toxoplasmosis presents a significant health challenge with a critical need for effective antimicrobial therapies.
- Existing research is limited by the lack of advanced human-in vitro models, hindering therapeutic development.
Purpose of the Study:
- To establish a novel human retinal organoid model for studying ocular toxoplasmosis.
- To investigate the susceptibility and response of human retinal organoids to *Toxoplasma gondii* infection.
Main Methods:
- Human induced pluripotent stem cells were differentiated into retinal organoids at two developmental stages.
- Organoids were exposed to live or heat-killed *Toxoplasma gondii* tachyzoites.
- Infection progression and host-parasite interactions were analyzed using immunolabeling and transcript analysis (parasite and human cytokine genes).
Main Results:
- Both developing and mature retinal organoids were susceptible to *T. gondii* infection.
- Live tachyzoites spread throughout the organoids within one week, confirmed by *T. gondii* surface antigen 1 (SAG1) labeling.
- Infection induced significant changes in the expression of key parasite transcripts (SAG1, GRA6, ROP16) and human cytokine transcripts (CCL2, CXCL8, CXCL10, IL6).
Conclusions:
- The developed human retinal organoid model accurately represents ocular toxoplasmosis.
- This model provides a valuable platform for studying parasite-host interactions, disease mechanisms, and evaluating new drug candidates for ocular toxoplasmosis.
