Toxoplasma gondii Migration within and Infection of Human Retina

João M Furtado,Kathleen Mohs,Justine R Smith,Liam M Ashander,Binoy Appukuttan,Timothy J Chipps,Herbert B Tanowitz

doi:10.1371/journal.pone.0054358

João M Furtado, Kathleen Mohs + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0054358

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Journal: PloS one	Publication Date: Feb 21, 2013
Citations: 60	License type: CC BY 4.0

Affiliation: Oregon Health & Science University

Abstract

Toxoplasmic retinochoroiditis is a common blinding retinal infection caused by the parasite, Toxoplasma gondii. Basic processes relating to establishment of infection in the human eye by T. gondii tachyzoites have not been investigated. To evaluate the ability of tachyzoites to navigate the human retina, we developed an ex vivo assay, in which a suspension containing 1.5×107 parasites replaced vitreous in a posterior eyecup. After 8 hours, the retina was formalin-fixed and paraffin-embedded, and sections were immunostained to identify tachyzoites. To determine the preference of tachyzoites for human retinal neuronal versus glial populations, we infected dissociated retinal cultures, subsequently characterized by neuron-specific enolase or glial fibrillary acidic protein expression, and retinal cell lines, with YFP-expressing tachyzoites. In migration assays, retinas contained 110–250 live tachyzoites; 64.5–95.2% (mean = 79.6%) were localized to the nerve fiber layer, but some were detected in the outer retina. Epifluorescence imaging of dissociated retinal cultures 24 hours after infection indicated preferential infection of glia. This observation was confirmed in growth assays, with significantly higher (p≤0.005) numbers of tachyzoites measured in glial verus neuronal cell lines. Our translational studies indicate that, after entering retina, tachyzoites may navigate multiple tissue layers. Tachyzoites preferentially infect glial cells, which exist throughout the retina. These properties may contribute to the success of T. gondii as a human pathogen.

Highlights

Ocular toxoplasmosis is a common inflammatory eye disease that may complicate systemic infection with the parasite, Toxoplasma gondii [1]
1.25 million U.S residents suffer from ocular toxoplasmosis, and in certain parts of the world this eye disease is believed to affect over 15% of the population [2]
T. gondii tachyzoites migrate through human retina To evaluate the ability of T. gondii tachyzoites to migrate through human retina, we developed an ex vivo assay, in which a suspension containing 1.56107 tachyzoites replaced the vitreous in an intact posterior eyecup

Summary

Introduction

Ocular toxoplasmosis is a common inflammatory eye disease that may complicate systemic infection with the parasite, Toxoplasma gondii [1]. 1.25 million U.S residents suffer from ocular toxoplasmosis, and in certain parts of the world this eye disease is believed to affect over 15% of the population [2]. While the devastating effects on vision in immunocompromised patients and unborn children are often emphasized, it is important to recognize that numerically, the largest group seeking treatment for ocular toxoplasmosis consists of otherwise healthy adults [3]. Standard antimicrobial treatments may suppress growth of the parasite, but side effects are common and none of the available drugs achieve eradication of encysted parasites from the retina [6]

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