Retinal Pigment Epithelium Cells Promote the Maturation of Monocytes to Macrophages in vitro

Abstract

Proliferative vitreoretinopathy is characterized by excessive cell proliferation within the eye; retinal pigment epithelial (RPE) cells form the majority of proliferating cells and interact with infiltrating leukocytes including monocytes. The purpose of this study was to determine the effect of RPE cells on the maturation of monocytes to macrophages. The enriched monocyte fraction of peripheral blood mononuclear cells was either cultured with or without RPE cells. The expression of the maturation-associated antigen CD 16 on monocytes was assessed by flow cytometry, and the concentration of bioactive transforming growth factor-β (TGF-β) in the culture supernatant measured by mink lung epithelial cell (Mv1Lu) bioassay. The cellular density of CD 16 in terms of mean fluorescence intensity was significantly higher on monocytes in coculture with RPE cells (p = 0.0153) than on monocytes in monoculture. The CD 16 expression was significantly (p = 0.0093) reduced when antibodies to TGF-β were added to the culture medium. RPE cells did not express CD 16. Supernatants from cocultures also contained active TGF-β (76.7 ± 23.8 pg/ml), while in those of cell monocultures TGF-β was close to the detection limit. We conclude that RPE cells stimulate and modulate the differentiation of monocytes to macrophages. Bioactive TGF-β generated in the coculture was in part responsible for this effect. It seems likely that RPE cells or interactions between RPE cells and monocytes could be an important factor in inflammatory/immune processes and wound healing in the eye, which are probably involved in proliferative vitreoretinopathy.