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Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis

When a person becomes infected with Toxoplasma gondii, ocular toxoplasmosis is the most common clinical presentation. The medical literature describes retinitis with surrounding hyperpigmentation secondary to proliferative changes in the retinal pigment epithelium, which is sufficiently characterist...

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Autores principales: Lie, Shervi, Vieira, Bárbara R., Arruda, Sigrid, Simões, Milena, Ashander, Liam M., Furtado, João M., Smith, Justine R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843916/
https://www.ncbi.nlm.nih.gov/pubmed/31569536
http://dx.doi.org/10.3390/microorganisms7100405
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author Lie, Shervi
Vieira, Bárbara R.
Arruda, Sigrid
Simões, Milena
Ashander, Liam M.
Furtado, João M.
Smith, Justine R.
author_facet Lie, Shervi
Vieira, Bárbara R.
Arruda, Sigrid
Simões, Milena
Ashander, Liam M.
Furtado, João M.
Smith, Justine R.
author_sort Lie, Shervi
collection PubMed
description When a person becomes infected with Toxoplasma gondii, ocular toxoplasmosis is the most common clinical presentation. The medical literature describes retinitis with surrounding hyperpigmentation secondary to proliferative changes in the retinal pigment epithelium, which is sufficiently characteristic that investigation often is not needed to make the diagnosis. We aimed to establish the frequency of “typical” ocular toxoplasmosis and delineate its molecular basis. Among 263 patients presenting consecutively with ocular toxoplasmosis to Ribeirão Preto General Hospital in Brazil, where T. gondii infection is endemic, 94.2% of 345 eyes had retinal hyperpigmentation. In ARPE-19 and primary human retinal pigment epithelial cell monolayers exposed to minimal numbers of T. gondii tachyzoites, the proliferation marker–KI-67–was increased in uninfected cells, which also were rendered more susceptible to infection. RT-qPCR and ELISA detected increased expression of vascular endothelial growth factor A (VEGF) and insulin-like growth factor (IGF)1, and decreased expression of thrombospondin (TSP)1 by infected cells. Blockade of VEGF and IGF1—or supplementation of TSP1—reversed the proliferation phenotype in uninfected cells. Our findings confirm that hyperpigmentation is a characteristic feature of retinitis in ocular toxoplasmosis, and demonstrate that T. gondii-infected human retinal pigment epithelial cells secrete VEGF and IGF1, and reduce production of TSP1, to promote proliferation of adjacent uninfected cells and create this disease-specific appearance.
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spelling pubmed-68439162019-11-25 Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis Lie, Shervi Vieira, Bárbara R. Arruda, Sigrid Simões, Milena Ashander, Liam M. Furtado, João M. Smith, Justine R. Microorganisms Article When a person becomes infected with Toxoplasma gondii, ocular toxoplasmosis is the most common clinical presentation. The medical literature describes retinitis with surrounding hyperpigmentation secondary to proliferative changes in the retinal pigment epithelium, which is sufficiently characteristic that investigation often is not needed to make the diagnosis. We aimed to establish the frequency of “typical” ocular toxoplasmosis and delineate its molecular basis. Among 263 patients presenting consecutively with ocular toxoplasmosis to Ribeirão Preto General Hospital in Brazil, where T. gondii infection is endemic, 94.2% of 345 eyes had retinal hyperpigmentation. In ARPE-19 and primary human retinal pigment epithelial cell monolayers exposed to minimal numbers of T. gondii tachyzoites, the proliferation marker–KI-67–was increased in uninfected cells, which also were rendered more susceptible to infection. RT-qPCR and ELISA detected increased expression of vascular endothelial growth factor A (VEGF) and insulin-like growth factor (IGF)1, and decreased expression of thrombospondin (TSP)1 by infected cells. Blockade of VEGF and IGF1—or supplementation of TSP1—reversed the proliferation phenotype in uninfected cells. Our findings confirm that hyperpigmentation is a characteristic feature of retinitis in ocular toxoplasmosis, and demonstrate that T. gondii-infected human retinal pigment epithelial cells secrete VEGF and IGF1, and reduce production of TSP1, to promote proliferation of adjacent uninfected cells and create this disease-specific appearance. MDPI 2019-09-29 /pmc/articles/PMC6843916/ /pubmed/31569536 http://dx.doi.org/10.3390/microorganisms7100405 Text en © 2019 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lie, Shervi
Vieira, Bárbara R.
Arruda, Sigrid
Simões, Milena
Ashander, Liam M.
Furtado, João M.
Smith, Justine R.
Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title_full Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title_fullStr Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title_full_unstemmed Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title_short Molecular Basis of The Retinal Pigment Epithelial Changes That Characterize The Ocular Lesion in Toxoplasmosis
title_sort molecular basis of the retinal pigment epithelial changes that characterize the ocular lesion in toxoplasmosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843916/
https://www.ncbi.nlm.nih.gov/pubmed/31569536
http://dx.doi.org/10.3390/microorganisms7100405
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