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M. Narayan, J. Joseph, B. Little, F. Gonzalez–Fernandez; Immunohistochemical Study of Murine Transgenic Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3550.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoblastoma may represent a informative model to study cell–fate determination in the retina. Human retinoblastomas have been shown to arise from a pluripotential stem cell that defaults along a cone phenotype (Gonzalez–Fernandez et al., Am. J. Pathol. 1992,141:363–75). Further characterization of the mechanism responsible for this default pathway toward cone gene expression could potentially be better studied in a transgenic model of retinoblastoma. Purpose: To determine the expression profile of the ocular tumors in transgenic mice expressing SV 40 T antigen in the retina. Methods: The transgenic mice were the gift of Dr. Daniel Albert. Globes were collected from SV 40 T antigen positive mice at 1, 4, 6 months of age. All tissues were fixed in 4% paraformaldehyde. One eye was embedded in paraffin for immunohistochemistry by the Avidin–Biotin Complex (ABC) method. The other eye was processed for frozen sections to be used for immunofluorescence. The antibodies were directed against: IRBP, cone and rod opsins, cone and rod transducins, cone arrestin (photoreceptors); HPC–1 (amacrine cells); Thy 1.1 (ganglion cells); calbindin (horizontal cells); SV 40 T antigen. Results: Hematoxylin & eosin stains of sections showed scattered malignant cells in the inner nuclear layer of the retina at one–month of age. Their nuclei were positive for SV 40 T antigen. In older tumors, Homer–Wright rossettes were common. In contrast, Flexner–Wintersteiner rossettes were never observed. Staining for IRBP was distinct and had a vesicular cytoplasmic pattern which was often polarized toward one end of the cell. The tumors were also positive for cone opsin. Undifferentiated tumor cells demonstrated staining of the plasmalemma. Cone opsin staining was also appreciated in the central region of the Homer–Wright rossettes. The other antibodies tested to–date showed only non–specific reactivity. Conclusions: The intraocular tumors of the SV 40 T antigen mice arise from a malignant cell initially situated in the inner nuclear layer. From this early stage of tumor development through advanced stages, the malignant cells are similar to that in humans, in that they default along a cone phenotype.
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