December 1998
Volume 39, Issue 13
Free
Articles  |   December 1998
Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.
Author Affiliations
  • N A Syed
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • J J Windle
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • S R Darjatmoko
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • J M Lokken
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • R A Steeves
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • R Chappell
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • I H Wallow
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • B A Koop
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • G Mangold
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • K A Howes
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
  • D M Albert
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
Investigative Ophthalmology & Visual Science December 1998, Vol.39, 2800-2805. doi:
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    • Get Citation

      N A Syed, J J Windle, S R Darjatmoko, J M Lokken, R A Steeves, R Chappell, I H Wallow, B A Koop, G Mangold, K A Howes, D M Albert; Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.. Invest. Ophthalmol. Vis. Sci. 1998;39(13):2800-2805.

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

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Abstract

PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

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