CHARACTERIZATION OF INTRAOCULAR TUMORS ARISING IN TRANSGENIC MICE

Purpose. To characterize intraocular tumors that arise by in situ tran sformation in the choroid-retinal pigment epithelium (RPE) in transgen ic mice bearing the SV40 oncogene under the control of the mouse tyros inase promoter. Methods. Tumors from TySV40 transgenic mice were chara cterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. Tumor cell lines were established and charac terized for growth and metastatic potential in the eyes of nude mice. Results. On light microscopy, ocular tumors were predominantly epithel ioid, although occasional clusters of spindle cells were also present. Transmission electron microscopy revealed the presence of numerous ba sal infoldings and abundant multilaminated basement membranes on the o cular tumors. Tumors stained with antibodies to melanoma-associated an tigens, gangliosides GD2 and GD3, and the SV40 T antigen. Radiolabeled transgenic tumor cells preferentially localized in the liver after in travenous injection in normal mice. Intracamerally transplanted transg enic tumors metastasized from the eyes to the livers of nude mice. Con clusions. In TySV40 transgenic mice, intraocular tumors develop that a rise at the choroid-RPE interface, and they display morphologic and ul trastructural features consistent with RPE carcinomas. However, the tr ansgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal mela nomas. The TySV40 transgenic murine tumors represent potentially usefu l tools for investigations into the biology and metastasis of intraocu lar neoplasms.