Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing

Abstract

Retinoblastoma is a rare cancer that occurs during childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy, which is known to increase the risk of secondary cancers in genetically predisposed patients. Multimodality therapy (usually intravenous but also intra-arterial and intravitreal chemotherapy, transpupillary thermotherapy, cryotherapy, or brachytherapy) has recently improved the eye salvage rate in retinoblastoma and has led to a decreased need for external beam radiotherapy. However, the treatment of advanced intraocular retinoblastoma remains a real challenge, especially in cases of vitreous and subretinal seeding. There is a need for alternative and less toxic therapies as well as for better ways to administer the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper describes the different xenograft rodent models published in the literature so far. We will also describe a new orthotopic xenografted retinoblastoma model in immunodeficient mice, which is suitable for preclinical assays. The xenograft model was established from tumor tissue obtained directly from surgical samples and closely mimics human retinoblastoma.

Keywords: Histological analysis; Patient-derived xenografts; Retinoblastoma; Xenograft rodent models.

Fig. 1

Orthotopic xenograft procedure.

Fig. 2

Histological analysis of a mouse eye showing a massive infiltration of the retina as well as the vitreous and anterior chambers by retinoblastoma tumor cells.

Fig. 3

Fundus photography and OCT of mouse eyes after orthotopic xenograft of retinoblastoma showing two retinal tumors; one retinal tumor starts to invade the vitreous (images using Micron IV, Phoenix Research Labs).