Dahlia Perez, Jacqueline Lees
Uveal melanoma (UM) is the most common adult primary eye tumor, and though successful treatments exist for the primary tumor, half of UM patients develop metastases within 15 years at which time their average survival is 6 months. Therefore, a desperate need exists for improved understanding and treatment of this disease. We have generated a model of UM in zebrafish driven by the same genetic changes that are responsible for inducing human UMs, specifically activating mutations in the GNAQ/GNA11 genes. In combination with other cancer-causing mutations, our fish develop melanomas with high frequency and die of this disease.
The picture above displays a representative example of tumors developing in the eye of our transgenic zebrafish model of UM. Based on the view from this angle of incision, the normal anatomy of the zebrafish eye will begin with the lens at the left side (or bottom in this picture) and proceed across the retina in ordered layers of various nerve and photoreceptor cells before finally ending in two pigmented cell layers. It is in the second of these pigmented layers, called the choroid, that the cancer forms in both the human malignancy and in the transgenic fish pictured. In the effort to study and understand this disease, the occurrence of tumors such as these not only substantiates our model, but provides a platform in which we may elucidate the mechanisms behind this malignancy.