6005

Purpose: Cytokines are soluble secreted proteins that play a crucial role in angiogenesis, apoptosis, immune response and cell proliferation and differentiation. Several studies have shown that uveal melanoma (UM) cells express a large number of cytokines that are involved in tumor progression and are considered poor prognostic markers. The purpose of this study is to evaluate the simultaneous expression of various cytokines in the vitreous of an albino rabbit model of UM. Methods: Vitreous samples from an immunosuppressed rabbit model of UM were taken at the time of animal sacrifice throughout the twelve-week model. Ten vitreous samples were used in the cytokine assay (RayBiotech, Georgia, USA). The samples were diluted by 50% with 1x Blocking Buffer and the assays were run as per manufacturers specifications. The membranes were then exposed to Kodak x-omat AR film for 20 to 40 seconds to detect chemiluminescence. The relative intensity of the signal was subsequently rated. Results: Expression of six cytokines, including macrophage migration-inhibitory factor (MIF), tissue inhibitor of metalloproteinase-1 (TIMP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), interferon-gamma (IFN- γ) and macrophage chemotactic protein-1 (MCP-1), was detected in the vitreous samples. Of the six cytokines detected, MIF, TIMP-1 and EGF were consistently highly expressed in all samples. Of the remaining cytokines, IFN-γ was detected in six samples, VEGF was detected in four samples, and MCP-1 was detected in one sample. Conclusions: Using an animal model of uveal melanoma, this study has identified the expression of various cytokines in the vitreous, an essential component within the ocular microenvironment, which may influence the progression of intra-ocular tumors. Further studies are warranted to investigate the role of these cytokines particularly MIF, TIMP-1 and EGF in UM progression.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]