Abstract
Purpose :
Retinoblastoma is the most common primary intraocular tumor in children. Its management is still a challenge. If preclinical models are helpful to evaluate new therapies, current retinoblastoma ones usually fail to represent the entire spectrum of the disease.
We thus aim to develop an orthotopic preclinical model of retinoblastoma using patient-derived tumor cells, mimicking different clinical presentations and available for the evaluation of new therapies.
Methods :
Subcutaneous retinoblastoma patient-derived (from enucleation) xenografts were established and maintained on immunodeficient Nude mice. To develop the orthotopic model, a suspension of retinoblastoma cells (from subcutaneous mice tumors) were injected in the subretinal space of Nude rat eyes. Tumor growth was assessed in vivo by retinal photographs and optical coherence tomography (OCT). At the end of the follow-up, histopathology analysis was performed. All experiments were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and the institutional guidelines and local ethics committee regarding animal experimentation.
Results :
Forty-nine eyes were grafted. Tumoral growth was observed in 49% of the eyes in a median time of 1,9 weeks. Media remained clear in nearly all eyes, allowing a high-quality observation of fundus during follow-up. OCT documented different patterns of tumoral growth: subretinal, intraretinal or vitreous growth. Interestingly, in some cases the tumors initially located under the retina has migrated secondarily into the inner retina, the usual location of emergence of retinoblastoma in children. Histopathology confirmed the presence of retinoblastoma viable cells.
Conclusions :
We develop a preclinical model of retinoblastoma in Nude rat eyes, by grafting under the retina patient-derived tumor cells. The rate of tumor growth must be improved but the model demonstrated subretinal, intraretinal or vitreous tumors and is adapted to new retinoblastoma treatment evaluation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.