A Rabbit Model of Retinoblastoma: Tumor Induction, Imaging Characterization, and Translational Applications

Objective: Preclinical models of retinoblastoma are critical for investigating tumor biology and assessing emerging therapeutic and imaging approaches. However, currently available small-animal models are constrained by anatomical limitations and reduced translational relevance. This study aimed to develop a proof-of-concept rabbit model of retinoblastoma (RB) and to characterize tumor progression using multimodal imaging and histopathological confirmation. Methods: Human retinoblastoma cells (WERI-Rb-1) were aseptically injected into the subretinal space of New Zealand White rabbits. Tumor development was monitored longitudinally using indirect ophthalmoscopy, color fundus photography, , and slit-lamp biomicroscopy with a +78 diopter lens. Imaging findings were confirmed with histopathological features following enucleation. Results: Tumor formation was successfully achieved in 77.8% of eyes (7/9), with a mean latency period of 4.1 days (4-5 days). Progressive growth was characterized by a well-defined subretinal mass with focal vitreous seeding. Multimodal imaging enabled noninvasive visualization of tumor architecture and vascular features, with descriptive concordance between imaging findings and histopathological features. Histologically, tumor cells were arranged in sheets with hyperchromatic nuclei, a high nuclear-to-cytoplasmic ratio, and focal rosette-like structures. Synaptophysin positivity supported neuroendocrine differentiation and confirmed the retinoblastoma phenotype. Conclusions: This study demonstrates the feasibility of establishing a proof-of-concept rabbit model of retinoblastoma, with clinical, imaging, and histopathological features consistent with the disease. Further validation in larger cohorts is needed to establish the consistency and generalizability of the model.