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Andrea Wenzel, Brian Samuels, Timothy Corson; Optical coherence tomography for screening of orthotopic retinoblastoma xenografts. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3967.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoblastoma is the most common intraocular tumor in children, often causing blindness. Orthotopic xenograft models are a critical tool for studying new therapeutic methods. A successful xenograft model has been generated by intravitreal injection of newborn rats with a bioluminescent derivative of the Y79 human retinoblastoma cell line. Although this model is powerful, screening panels of xenografts from multiple cell lines would be valuable for assessing inter-individual responses to novel therapeutics. We evaluated whether optical coherence tomography (OCT) could be used to identify successful xenografts of other, non-engineered retinoblastoma cell lines and characterize xenograft growth patterns.
Sprague-Dawley rats (P0) received an intravitreal injection of 1,000 to 250,000 retinoblastoma cells from either the standard bioluminescent/EGFP+ Y79 cell line or other, non-engineered retinoblastoma cell lines. The Micron III rodent imaging system was used to obtain fundus photographs and OCT images regularly over the course of 4 weeks to document xenograft development.
Using in vivo, intraocular, EGFP fluorescence imaging as a guide, previously described Y79-EGFP-luciferase xenografts were characterized by OCT. The xenografts produced both small and large tumors that were typically dense, highly vascularized, and had well-defined edges. While direct retinal involvement was rare, xenografts appeared to preferentially grow just posterior to the lens suggesting that the regressing tunica vasculosa lentis and/or the regressing hyaloid artery may be the preferred vascular source. Successful non-fluorescent xenografts had similar morphologic characteristics and growth patterns to those from the Y79 line on OCT imaging.
OCT imaging of retinoblastoma orthotopic xenografts is a novel way to spatially analyze and follow tumor growth in vivo. When tumors were not always readily evident on brightfield imaging, OCT proved to be a valuable tool to help identify hard-to-see, non-fluorescent tumors generated with these non-engineered retinoblastoma cell lines. This approach will enable rapid screening of additional cell lines in the future as well as quantitative spatial analysis of response to therapeutics.
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