Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma

PURPOSE: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options....

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Autores principales: Wenzel, Andrea A., O’Hare, Michael N., Shadmand, Mehdi, Corson, Timothy W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440496/
https://www.ncbi.nlm.nih.gov/pubmed/25999678
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author Wenzel, Andrea A.
O’Hare, Michael N.
Shadmand, Mehdi
Corson, Timothy W.
author_facet Wenzel, Andrea A.
O’Hare, Michael N.
Shadmand, Mehdi
Corson, Timothy W.
author_sort Wenzel, Andrea A.
collection PubMed
description PURPOSE: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development. METHODS: The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis. RESULTS: Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous. CONCLUSIONS: OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.
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spelling pubmed-44404962015-05-21 Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma Wenzel, Andrea A. O’Hare, Michael N. Shadmand, Mehdi Corson, Timothy W. Mol Vis Research Article PURPOSE: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development. METHODS: The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis. RESULTS: Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous. CONCLUSIONS: OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model. Molecular Vision 2015-05-01 /pmc/articles/PMC4440496/ /pubmed/25999678 Text en Copyright © 2015 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Wenzel, Andrea A.
O’Hare, Michael N.
Shadmand, Mehdi
Corson, Timothy W.
Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title_full Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title_fullStr Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title_full_unstemmed Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title_short Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma
title_sort optical coherence tomography enables imaging of tumor initiation in the tag-rb mouse model of retinoblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440496/
https://www.ncbi.nlm.nih.gov/pubmed/25999678
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