Orthotopic xenografts in ocular tumors

Abstract

AbstractIn order to allow pharmacological assessment of innovative intraocular treatments in more relevant and predictive models, we have developed preclinical orthotopic xenografts of both primary human uveal melanoma (UM) and retinoblastoma (Rb) into immunodeficient mice. Orthotopic models of human UM and Rb have been developed from subcutaneous xenografts previously established and characterized in the laboratory. Mice bearing xenografts were sacrificed and tumors were dissected and injected into the subretinal space of SCID mice. After sub‐retinal injection, ophthalmic examination of the mice was performed weekly. When tumor cells invaded vitreal cavity and anterior chamber, the mice were sacrificed for ophthalmological pathological analyses. The RB200 model, was used for preclinical trial validation.After orthotopic transplantation, pathological analyses confirmed the conservation of histological sub‐type of the primary tumor, i.e. epithelioid and/or spindle cell, than in corresponding patient’s tumors and subcutaneous xenografts.For retinoblastoma, the orthotopic xenograft showed similar clinical and pathological similarities to human tumors. Theses models are suitable for preclinical trial.