Abstract
Purpose:
Retinoblastoma is the most common intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, there continues to be a high morbidity associated with these therapies and therefore 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 TAg-RB model has the closest molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Optical coherence tomography (OCT) has previously been used to characterize TAg-RB tumors in 10-13 week-old mice. Here, we evaluated whether OCT imaging could be used to document tumor growth in the TAg-RB model at 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 regularly from 2 to 20 weeks of age to document tumor development. Tumor morphology was confirmed by histological analysis.
Results:
Light-colored, intraretinal tumors, preferentially in the periphery, were readily seen by funduscopy in animals ≥8 weeks of age. By OCT, hyperreflective tumor masses arising in the inner nuclear layer were evident as early as five weeks, even when no pathology was yet evident by funduscopy. These masses grew into discrete, discoid tumors that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous.
Conclusions:
OCT is a novel, non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we were able to characterize tumor growth as early as 5 weeks, corresponding to the earliest stages at which tumors are histologically evident, and before they are evident by funduscopy. Tracking tumor growth from its very earliest stages will allow better analysis of the efficacy of novel therapeutics tested in this powerful mouse model.
Keywords: 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) •
703 retinoblastoma •
551 imaging/image analysis: non-clinical