Ординатура / Офтальмология / Английские материалы / Ocular Oncology_Albert, Polans_2003

1.Rabbit Model Using Greene Melanoma Cells

Krohn and collaborators described the successful transplantation of Greene melanoma cells into the posterior ocular segment of rabbits in 1970 [98]. These investigators used amelanotic Greene melanoma that was maintained in the AC of rabbits [98]. After AC implantation, the tumor grew rapidly and ruptured the globe within 12 to 14 days. Pieces of this tumor were then transplanted into the subchoroidal space of New Zealand albino rabbit eyes. Tumor growth occurred in most of the animals and was ophthalmoscopically detectable within 16 days [98]. In 1982, Liu and collaborators used a rabbit model with implanted hamster Greene melanoma grown in the choroid of the eye [99], using the implantation procedure of Krohn and collaborators [98]. The tumor grew and was clinically recognizable 4 to 6 weeks after implantation. After an additional 6 to 8 weeks, the tumor-bearing eye perforated, and at the 10th week after implantation, the rabbits exhibited weakness and loss of body weight. Necropsies revealed widespread metastases, including metastases in the liver [99]. The histopathological appearance of the metastatic tumor was identical to that of the primary choroidal Greene melanoma. Most tumor cells in the metastatic lesion appeared to be epithelioid and showed marked pleomorphism [100]. Other techniques for subchoroidal implantation of Greene melanoma were subsequently developed [101]. Lambrou and collaborators used a transvitreal approach to deposit a tumor fragment into the subchoroidal space of rabbits [102].

Greene melanoma transplanted into the eyes of rabbits has been used for evaluation of treatment effects on intraocular tumor. These studies have included anticancer agents [103,104], ionizing radiation [105,106], ferromagnetic hyperthermia combined with iodine-125 brachytherapy [107], hyperthermia [108], photodynamic therapy on choroidal tumors [109,110], photoradiation treatment [111], fluorouracil therapy [112], indocyanine green–enhanced diode laser treatment [113], and phototherapy of AC tumors [114].

2.Rabbit Model Using B16 Melanoma Cells

Inoculation of B16 melanoma into the rabbit requires immunosuppression in order to enable tumor growth. Inoculation of B16F10 melanoma into the subchoroidal space in rabbits treated with cyclosporin A results in tumor growth [115,116]. These globes are usually half filled with tumor by the third week and totally filled with tumor by the fourth week after implantation [115]. Grossly visible metastatic lesions are present only in the lung, consistent with the metastatic pattern seen with B16F10 melanoma when grown in the syngeneic host [115]. In a study using murine cutaneous B16F10 melanoma cells, hamster cutaneous melanoma, and human uveal melanoma cell lines transplanted into the subchoroidal space of the rabbit eyes, the B16F10 line was the only source that consistently generated heavily pigmented choroidal tumors [115]. A rabbit model of extrascleral extension of ocular melanoma has also been established [116].

A major disadvantage of this rabbit model is the requirement of daily injections, of cyclosporin A, which limits the time the animal can be kept for observation. Cyclosporin-treated rabbits usually die within 6 to 10 weeks. To date, the only melanoma cell line successfully implanted in the rabbit eye without immunosuppression is the amelanotic Greene hamster melanoma.

3.Rabbit Model Using Human Uveal Melanoma

Kann-Mitchel and coworkers observed that the addition of cyclosporin A improves the growth and survival of human uveal melanoma cell lines in the AC of rabbit eyes [80]. Ligget and collaborators successfully established human uveal melanoma xenografts in the choroid of immunosuppressed rabbits [117]. These authors noted spontaneous disappearance of the tumor over a 2-week period when the immunosuppression was discontinued.

F.Chick Embryo Model

Luyten and coworkers injected cultured human uveal melanoma cells into the chicken embryonal eye at a stage when the immune system was not mature. The melanoma cells were accepted as part of the organism by the host. Tumors were found in 20% of the embryos injected with uveal melanoma. The eyes were removed on the 19th embryonal day and did not exhibit abnormal development as a result of the injection [118].

VII. SUMMARY

Various animal models of human uveal melanoma have been studied. Each of these models has unique advantages and disadvantages. Spontaneous uveal melanoma rarely occurs in dogs and cats. The occurrence of these tumors is unpredictable. Chemicalor radiation-induced intraocular pigmented tumors may be of RPE. Feline leukemia-sarcoma virus-and simian virus 40-induced uveal proliferations fail to metastasize. The biological behavior of Greene and B16 melanoma cell lines after intraocular injection into various animal species is predictable, allowing for study of mechanisms of growth and metastasis. The pathogenesis of intraocular pigmented tumors in transgenic mice is beginning to be understood and offers promise as a model for studying growth and metastasis, with the potential for developing more effective treatments.

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