Clinical and Histopathological Characterization of a New Xenograft Model of Vitreous Seeding of Human Intraocular Retinoblastoma

Abstract

Abstract: : Purpose: To describe a new xenograft model of diffuse vitreous seeding of human retinoblastoma in the nude rat eye. This xenograft model uses early passage human retinoblastoma cell lines that grow naturally as sphereules in suspension culture. This growth characteristic closely mimics naturally occurring vitreous seeding, a late stage feature that is difficult to treat successfully in human eyes. Methods: We injected the vitreous of one eye of each of 18 nude rats with a human retinoblastoma cell line (CHLA203). The animals were followed clinically by indirect ophthalmoscopy and euthanized after 15, 30, 45, 60 and 75 days. Histopathology was performed in all of the injected eyes to confirm the clinical findings, and the brain, liver, mediastinum and lungs were also examined for metastasis. Results: 2 animals were euthanized early in the study due to complications of the injection procedure and loss of fundus view. The tumor implantation rate was of 65% and the clinical assessment of intraocular tumor growth was possible throughout the follow-up period of 2.5 months, with pupillary dilation and conventional indirect fundus ophthalmoscopy. The vitreous seeds could be detected in the model 3 weeks after injection, and progressed to vitreous clumps towards the posterior pole. Intraretinal and subretinal masses were present at 6 weeks, anterior chamber infiltration at 8 weeks, and extensive subretinal involvement and exudative retinal detachment by 10 weeks after tumor cell injection. The histopathology confirmed the clinical diagnosis and different stages of progression, but did not reveal metastasis to the studied organs. Conclusions: The xenograft model of retinoblastoma in nude rats closely resembles the vitreous seeding stages of the human disease. Since human eyes with vitreous seeding are difficult to salvage with current therapy, the model described here may provide the opportunity for evaluation of a large number of promising therapies for late-stage intraocular disease.

Keywords: retinoblastoma • vitreous • animal model