Animal models of uveal melanoma

Abstract

Many attempts have been made to develop a suitable animal model to study more effectively the aetiology, pathogenesis, diagnosis and therapy of intraocular (uveal) melanoma. Uveal melanoma may spontaneously occur in some animals, including dogs, cats, horses, rats, mice, birds and fish. The histological features, metastatic behaviour and unpredictable nature of occurrence of these uncommon spontaneous tumours detract from their suitability as a model. Several methods have been developed to induce intraocular melanoma chemically or by radiation in laboratory animals. Some of these induced tumours resemble human uveal melanoma, although the majority originate from the retinal pigment epithelium. Uveal proliferations have been biologically induced by feline leukaemia/sarcoma virus and simian virus 40, although the presence of virus in tumour cells and extraocular tumours resulting from shed virus detract from the utility of this model. Inoculation of tissue culture hamster, murine or human melanoma cells into animal eyes has the advantage that the inoculation site and size of inoculum can be controlled. Disadvantages include the immune suppression necessary for tumour growth in some models as well as the fact that many of the melanoma cell lines are of cutaneous origin. Transgenic murine models have been developed using the promoter region of the tyrosinase gene to target expression of oncogenes in melanin-producing cells. Spontaneous intraocular pigmented tumours and distant metastases may occur, although many, if not all, of the intraocular tumours arise in the retinal pigment epithelium.