Transforming growth factor-β regulates human retinal pigment epithelial cell phagocytosis by influencing a protein kinase C-dependent pathway

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Abstract
• Background: Transforming growth factor-β (TGF-β) plays an important role in the pathogenesis of many ocular diseases, including proliferative vitreoretinopathy. We examined the effect of TGF-β on the phagocytosis of rod outer segments by retinal pigment epithelium (RPE), which is a major function of RPE, and investigated the dependence of this effect on the protein kinase C (PKC) pathway. • Methods: Phagocytotic uptake of fluoresceinated bovine rod outer segments was determined by flow cytometry. RPE cells were treated with TGF-β1 or TGF-β2 and their effects on phagocytosis were examined. The effects of various PKC inhibitors (calphostin C, staurosporine, and extended exposure to phorbol 12-myristate 13-acetate, PMA) and a stimulator (brief exposure to PMA) on RPE phagocytosis was evaluated. • Results: Both TGF-β1 and TGF-β2 up-regulated RPE phagocytosis and PMA abolished the upregulating effect of TGF-β. In contrast, PKC inhibition by staurosporine and calphostin C resulted in increased phagocytosis. A combination of TGF-β and PKC inhibitor treatment did not produced any additive effect on phagocytosis. • Conclusion: We concluded that TGF-β up-regulates human RPE phagocytosis, but that this effect is counteracted by PKC activation. It is possible that this TGF-β-induced effect is due, in part, to a negative modulation of the PKC-dependent pathway.

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