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Karin U Loeffler, Marta M Kilian, Frank G Holz, Thomas Tüting, Martina C Herwig; Morphologic and immunohistochemical features in the ageing Hgf-Cdk4 mouse eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5071.
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© ARVO (1962-2015); The Authors (2016-present)
Searching for an animal model of spontaneous or inducible uveal melanoma, we evaluated the ocular findings in an established mouse model of spontaneous skin melanoma with melanocytic proliferation and knock-out of a tumour suppressor gene (Hgf-Cdk4). This should also further clarify the role and impact of hepatocyte growth factor/scatter factor/deregulated receptor tyrosine kinase and cyclin-dependent kinase 4 on ocular melanocytes in comparison with dermal melanocytes.
In total, 15 Hgf-Cdk4 mouse eyes were investigated, the emphasis being on the aged eye (11 months, n=12), and were compared with three 10 months old eyes from "regular" C57Bl/6 mice with a similar genetic background. Step sections were stained with H&E and PAS, and sections inbetween were labeled with antibodies (Abs) to Ki67 (proliferation marker), MART1 ('melanoma antigen') and F4/80 (macrophages). Prior to immunohistochemistry (IH), sections were bleached for better visualization of the chromogen (AEC).
Morphologically, the most marked difference in melanocyte-modified mouse eyes was the appeareance of heavily pigmented cells in the anterior corneal stroma and along the chamber angle. No significant increase in epithelial pigmentation of either corneal or conjunctival epithelium was noted. Unequivocal proliferation of uveal melanocytes or RPE cells was also not observed however, the choroid appeared even somewhat less pigmented than in C57Bl/6 mice with some conspicuous cellular features. IH so far showed no significant difference in labeling between Hgf-Cdk4 and C57Bl/6 mouse eyes, and surprisingly, using our 3 Abs, the origin of the pigmented corneal cells (or the pigment) remains unclear. Also, Ki67 was negative while the overlying corneal/conjunctival epithelium showed some proliferative activity in all specimens.
In Hgf-Cdk4 mouse eyes, no major difference in pigmentation or cellular components was observed in the ocular epithelium or in the posterior segment, and subtle findings so far were equivocal. Thus, although the Hgf-Cdk4 mouse develops spontaneous cutaneous melanomas, it does not qualify as a model for spontaneous conjunctival or uveal melanoma. However, remarkable changes regarding pigmentation were noted in the cornea and chamber angle in these animals, and further manipulation of the anterior segment might allow creating models of anterior segment tumors and possibly also glaucoma.
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