Retinoblastoma: Animal Models of Tumor Progression

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and of developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biologic behavior analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor progression similar to that seen in human metastatic disease. Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreal cavity. Tumors progressively invaded the retina, subretinal space, choroid and optic nerve head, and anterior chamber of the eye. Tumors progressed into the subarachnoid space and focally invaded the brain and contralateral optic nerve. Large tumors developed extraocular extensions. The histology of the tumors showed a poorly differentiated pattern with high mitotic rate, foci of necrosis, and calcification. The WERI-Rb model more closely resembled non-metastatic human retinoblastoma. WERIRb tumors were localized in the eye with only anterior choroidal invasion at late stages. To examine potential biological differences in vitro, the retinoblastoma cell lines were co-cultured with adherent choroid cells or adherent glioma cells which represent the targets of metastatic retinoblastoma in vivo. Consistent with the in vivo observations, Y79 cells but not WERI-Rb cells adhere specifically to both the choroidal and the glioma cell lines.