We have previously shown the importance of peri- and intratumoral lymphatic vessels for recurrence, metastasis, and prognosis in different ocular malignancies, specifically in CM.
8-10,22–26 Therefore, antilymphangiogenic therapies are needed to develop new therapeutic options. To study them, we need murine immune-competent models because for lymphangiogenesis, immune cells are closely interlinked.
27 However, to date there are no immune-competent mouse models to study the biology of CM and to test new therapeutic approaches.
28,29 In this study, we aimed to develop a new model for CM in immune-competent mice. In patients, CM growth is initiated within the epithelium and invasion across the basement membrane is a major indicator of malignancy. In our model, we are directly injecting tumor cells underneath the basement membrane, to mimic the clinicopathological situation. Similar to existing tumor models
30 in other anatomical sites of the eye,
31–33 this mouse model has its pros and cons. A major disadvantage might be the use of cutaneous and not primary CM cells, as it is not suitable for testing human antibodies or immune-mediated human therapies. However, due to the current lack of mouse CM cell lines and considering the fact that epidermis and conjunctiva show many similarities regarding embryonic origin, development, stratification, lymphatic drainage, and outer barrier to the environment, we consider cutaneous cell lines are currently one of the best options for tumor induction in immune-competent syngeneic mice. A similar approach for uveal melanoma is used in a mouse model developed by Lattier et al. and Dithmar et al.,
31–33 in which B16F10 cutaneous melanoma cells are injected in the posterior compartment of the eye. Another approach has been performed by De Waard et al.
30 Hereby, the authors inject human CM cells into severe combined immunodeficient (SCID) mice.