A Developmentally Appropriate Orthotopic Retinoblastoma Xenograft Model

Abstract

<div><p>(A) Injection of 1,000 cultured human retinoblastoma cells into the vitreal cavity of newborn rat eyes leads to retinoblastoma by two weeks of age. The rats do not require immunosuppression because they are immunonaive for the first 24 hours after birth. This is an ideal model for testing new drugs and for studying the retinoblastoma cancer stem cell properties.</p> <p>(B) Human retinoblastoma cells have been genetically engineered to express the luciferase reporter gene. A two-week-old rat that received an intravitreal injection of Y79-LUC cells at birth is shown. Y79-LUC cells are retinoblastoma cells that express the firefly luciferase gene under the control of a constitutive promoter (see [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020332#pmed-0020332-b16" target="_blank">16</a>]). At two weeks, the rat received an intraperitoneal injection of the luciferase substrate (luciferin). The fluorescence is directly proportional to the tumor volume and the number of cells in the tumor. By using the Xenogen imaging system, we can follow individual tumors as they grow and respond to chemotherapy.</p></div