Age and the Role of Macrophages in an Experimental Eye Tumor Model

Abstract

Purpose: : Previous studies described a different constitution of macrophages during the aging process of organisms. Since macrophages play an important role in tumor growth and eradication, we want to investigate their role in the process of eye tumor development in young and old mice.

Methods: : We studied the different macrophage constitution of young and old mice with mRNA expression for well-known macrophage markers. We used an intra-ocular tumor model by implanting B16F10 melanoma cells into the anterior chamber of the eye of a C57BL/6 mouse. We studied growth of the tumor, with the presence of macrophages and without (depletion is achieved by injecting clodronate liposomes subconjunctivally).

Results: : Old mice have a different intraocular macrophage constitution than young mice with a polarization towards the pro-angiogenic and immunosuppressive M2 type. While normal old mice developed large tumors, we observed a total inhibition of tumor growth in old mice after depletion of macrophages in the eye. Depletion of macrophages had no effect on tumor growth in young mice. Analysis with gene expression showed a typical M2 type profile in the blood and tumor eye of old mice.

Conclusions: : Old mice have a polarization towards an M2 type macrophage population. Removal of these macrophages in old mice leads to prevention of tumor growth. Further research is needed to show the clinical usefulness of macrophage depletion.

Keywords: oncology • immunomodulation/immunoregulation • aging