Retinoblastoma (Rb) is the most frequent primary intraocular tumour in children and if let untreated, can cause death. Preclinical animal models that mimic molecular, genetic, and cellular features of cancers are essential for studying cancer and searching for promising diagnosis and treatment modalities. There are several models described for Rb, but none of them fully met our requirements.
The aim of this study was to create a novel xenograft-nude mouse-model with broad application possibilities, which closely resembles the clinical observations and to investigate the development and spread of the tumour by using SLO/OCT as well as histology methods.
We injected human retinoblastoma Y79 cells intravitreally in both eyes of immune-deficient nude mice. The incidence of retinoblastoma as well as growth velocity were analysed 3, 6, 9 and 12 weeks after cell injection in vivo by SLO/OCT as well as ex vivo by electron microscopy (EM) and hematoxylin/eosin (HE) staining. Moreover, internal organs were histologically screened for potentially occurring metastases.
Already three weeks post-injection, animals developed a retinoblastoma. After five weeks tumour growth resulted in swelling of the eyes in individual animals and they showed a similar phenotype to that of untreated Rb patients at advanced stages of tumour-development. After 12 weeks, 67.5% of all analysed eyes (29 of 42) contained a retinoblastoma.
At early stages of Rb development, the SLO/OCT analysis correlated with the histology results. If the tumours were too large, only histological investigations were feasible.
The ultrastructural characteristics of the xenograft-tumours were very similar to those described for patient's tumours. In one mouse, brain metastases were observed.
Our retinoblastoma mouse model closely resembles the human disease. SLO/OCT can be used for the detection of Rb at early stages of development and could be used for monitoring of the success of future therapies.
- Received June 6, 2016.
- Accepted September 20, 2016.
- © 2016. Published by The Company of Biologists Ltd
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