December 2017
Volume 58, Issue 14
Open Access
Research Highlight  |   December 2017
A Novel Zebrafish Model for Studying Metastatic Behavior of Human Conjunctival Melanoma Cells
Author Affiliations
  • Michele C. Madigan
    Optometry and Vision Science, University of New South Wales and Save Sight Institute, University of Sydney, Sydney New South Wales, Australia; m.madigan@unsw.edu.au
Investigative Ophthalmology & Visual Science December 2017, Vol.58, 6072. doi:10.1167/iovs.17-23347
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      Michele C. Madigan; A Novel Zebrafish Model for Studying Metastatic Behavior of Human Conjunctival Melanoma Cells. Invest. Ophthalmol. Vis. Sci. 2017;58(14):6072. doi: 10.1167/iovs.17-23347.

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      © ARVO (1962-2015); The Authors (2016-present)

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Conjunctival melanoma (CM) is an uncommon but potentially sight- and life-threatening eye malignancy. Local CM is treated by surgical excision, and/or cryotherapy followed by adjuvant brachytherapy; proton radiotherapy; or chemotherapy (such as topical mitomycin C). Not all primary CM are excised successfully, and tumors may recur at the original site or at different locations across the conjunctiva, with local recurrence rates of up to 60% of patients after 5 years.1 CM may progress to metastatic disease, which is seen in approximately 40% of patients within 5 years; the 10-year melanoma-related death rate is reported as 9% to 35%.2 Treatments for CM patients with metastatic disease are mostly ineffective, and the outlook for patient survival is poor.1,2 A major challenge for managing CM is the rarity of the tumor, so that prospective large-scale clinical trials for current and emerging novel therapies are simply not feasible. As such, developing appropriate models of local and metastatic CM are important to complement real-world clinical experiences. In this issue of Investigative Ophthalmology & Visual Science, Pontes and colleagues3 describe a novel zebrafish xenograft model for studying the metastatic behavior of human CM cells, and for potentially testing new therapies that may target CM cells growing outside the eye environment. Using fluorescently labelled CM cells in transparent zebrafish provides an opportunity for whole body imaging and understanding of tumor cell migration patterns. The strategic injection of CM cells in the duct of Cavier in early development also means the model includes a developing innate immune system. The zebrafish model presented together with the available mouse models of metastatic CM, including a recent novel immune-competent CM mouse model with lymphangiogenic involvement,4 potentially provides an efficient and cost-effective approach to screening emerging novel therapies, including immunotherapies, that target metastatic CM cells. 
References
Lim L, Madigan MC, Conway RM. Conjunctival melanoma: a review of conceptual and treatment advances. Clin Ophthalmol. 2013; 7: 521–531.
Wong JR, Nanji AA, Galor A, Karp CL. Management of conjunctiva; malignant melanoma: a review and update. Expert Rev Ophthalmol. 2014; 9: 185–204.
Pontes KCS, Groenewoud A, Cao J, Ataide LMS, Snaar-Jagalska E, Jager MJ. Evaluation of (fli:GFP) Casper zebrafish embryos as a model for human conjunctival melanoma. Invest Ophthalmol Vis Sci. 2017; 58: 6065–6071.
Schlereth SL, Iden S, Mescher M, et al. A novel model of metastatic conjunctival melanoma in immune-competent mice. Invest Ophthalmol Vis Sci. 2015; 56: 5965–5973.
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