Animal models of uveal melanoma

Abstract

Animal models are crucial for the study of tumorigenesis and therapies in oncology research. Though rare, uveal melanoma (UM) is the most common intraocular tumor and remains one of the most lethal cancers. Given the limitations of studying human UM cells in vitro, animal models have emerged as excellent platforms to investigate disease onset, progression, and metastasis. Since Greene’s initial studies on hamster UM, researchers have dramatically improved the array of animal models. Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models. Inoculation techniques continue to be refined and expanded. Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis. Human UM cell lines have been used to generate rapidly growing xenografts. Most recently, patient-derived xenografts have emerged as models that closely mimic the behavior of human UM. Separate animal models to study metastatic UM have also been established. Despite the advancements, the prognosis has only recently improved for UM patients, especially in patients with metastases. There is a need to identify and evaluate new preclinical models. To accomplish this goal, it is important to understand the origin, methods, advantages, and disadvantages of current animal models. In this review, the authors present current and historic animal models for the experimental study of UM. The strengths and shortcomings of each model are discussed and potential future directions are explored.

Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model

“…Because of its rarity and the scarcity of intraocular tumor tissue for research, there is an urgent need to develop better models to study this devastating disease. In past studies, UM models have been most commonly performed on mice, rats, dogs, hamsters and rabbits [21][22][23][34][35][36]. While mice are considered the most cost-effective method [21,37], rabbits are preferred because of their large eye size, offering greater precision for inoculations and surgical manipulations [21,22,35,36].…”

“…In past studies, UM models have been most commonly performed on mice, rats, dogs, hamsters and rabbits [21][22][23][34][35][36]. While mice are considered the most cost-effective method [21,37], rabbits are preferred because of their large eye size, offering greater precision for inoculations and surgical manipulations [21,22,35,36]. Most importantly, they offer better visibility for macroscopic examination and allow for the use of conventional imaging techniques including ophthalmoscopy, ultrasound and OCT [21,24,25].…”

“…While mice are considered the most cost-effective method [21,37], rabbits are preferred because of their large eye size, offering greater precision for inoculations and surgical manipulations [21,22,35,36]. Most importantly, they offer better visibility for macroscopic examination and allow for the use of conventional imaging techniques including ophthalmoscopy, ultrasound and OCT [21,24,25]. Therefore, to better understand UM pathogenesis, we generated a rabbit UM animal model inoculated with human-derived cell lines.…”

“…While mice are the most widely utilized species for UM research owing to their low cost and ease of manipulation [20,21], rabbits have also been used because of their larger eye size compared to rodents and other small animals [21,22]. Histopathologically, ocular tumors formed in rabbits after injection of human UM cells into the suprachoroidal space closely mimic choroidal melanomas observed in patients, making it an ideal model to study primary UM [21,23,24]. Because of the heterotransplantation of human cell lines into rabbits, however, immunosuppression with cyclosporine A (CsA) is necessary despite it significantly decreasing the lifespan of animals [21,[24][25][26].…”

Need for a Dedicated Ophthalmic Malignancy Clinico-Biological Biobank: The Nice Ocular MAlignancy (NOMA) Biobank

“…To date, there is no curative treatment available for metastatic UM. Current animal models are scarce, especially metastatic models, and these do not allow for the generalization of the findings to humans [ 5 ]. Therefore, there is an urgent need to develop customized targeted treatments through collaborative translational and clinical research based on robust clinical, imaging, biological, and genetic data obtained from patients [ 6 ].…”