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

Wenzel AA, O'Hare MN, Shadmand M, Corson TW - Mol. Vis. (2015)

Bottom Line: 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.Tumor morphology was confirmed with histological analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Histology validates OCT findings. Examples of a 12-week and two 20-week T-antigen retinoblastoma (TAg-RB) eyes analyzed with funduscopy (A, E, I); optical coherence tomography (OCT) (B, F, J), OCT scale bars=100 µm; high-magnification hematoxylin and eosin (H&E; C, G, K); and low-magnification H&E (D, H, L), scale bars=200 µm. The lens is indicated with an asterisk (*).
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f3: Histology validates OCT findings. Examples of a 12-week and two 20-week T-antigen retinoblastoma (TAg-RB) eyes analyzed with funduscopy (A, E, I); optical coherence tomography (OCT) (B, F, J), OCT scale bars=100 µm; high-magnification hematoxylin and eosin (H&E; C, G, K); and low-magnification H&E (D, H, L), scale bars=200 µm. The lens is indicated with an asterisk (*).

Mentions: The tumors continued to increase in size at each weekly imaging session, and developed more irregular morphology over time. At 12 weeks, the tumors remained discrete ellipsoids (Figure 2 and Figure 3A, B). By 20 weeks, however, in many cases, the tumors had grown together, filling the vitreous by distorting the inner retina all the way to the posterior aspect of the lens (Figure 3E,F,I,J). Since proptosis was observed at this stage, the animals were euthanized for humane considerations.


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

Wenzel AA, O'Hare MN, Shadmand M, Corson TW - Mol. Vis. (2015)

Histology validates OCT findings. Examples of a 12-week and two 20-week T-antigen retinoblastoma (TAg-RB) eyes analyzed with funduscopy (A, E, I); optical coherence tomography (OCT) (B, F, J), OCT scale bars=100 µm; high-magnification hematoxylin and eosin (H&E; C, G, K); and low-magnification H&E (D, H, L), scale bars=200 µm. The lens is indicated with an asterisk (*).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440496&req=5

f3: Histology validates OCT findings. Examples of a 12-week and two 20-week T-antigen retinoblastoma (TAg-RB) eyes analyzed with funduscopy (A, E, I); optical coherence tomography (OCT) (B, F, J), OCT scale bars=100 µm; high-magnification hematoxylin and eosin (H&E; C, G, K); and low-magnification H&E (D, H, L), scale bars=200 µm. The lens is indicated with an asterisk (*).
Mentions: The tumors continued to increase in size at each weekly imaging session, and developed more irregular morphology over time. At 12 weeks, the tumors remained discrete ellipsoids (Figure 2 and Figure 3A, B). By 20 weeks, however, in many cases, the tumors had grown together, filling the vitreous by distorting the inner retina all the way to the posterior aspect of the lens (Figure 3E,F,I,J). Since proptosis was observed at this stage, the animals were euthanized for humane considerations.

Bottom Line: 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.Tumor morphology was confirmed with histological analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus