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Retinal pigment epithelial cell proliferation: Potentiation by monocytes and serum

  • Vitreo-Retinal
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Abstract

• Background: The development of proliferative vitreoretinopathy (PVR) results often from a breakdown of the blood-retina barrier and the intraocular accumulation of serum proteins and leukocytes, particularly monocytes, that then come into contact with retinal pigment epithelial (RPE) cells. To examine the effect of these two factors on RPE proliferation, which is characteristic of PVR, we used a coculture system of blood monocytes and human RPE cells. • Methods: RPE cells were incubated with a variable number of monocytes at different serum concentrations and assayed for proliferation by [3H]-thymidine incorporation and cell counting. To assess cell-cell communication, RPE cells were labeled with 2′,7′-bis(car-boxyethyl)-5(and 6) carboxyfluorescein acetoxy-methyl ester, and the dye transfer to monocytes was analyzed using an UV microscope. • Results: Monocytes (P<0.0004) and serum (P<0.0001), each on its own, significantly stimulated RPE cell growth, and these two variables were interrelated (P<0.0001), showing a potentiating synergism. In serum-free medium, monocytes increased proliferation to just above control levels, whereas the same number of monocytes in 5% serum increased the [3H]-thymidine incorporation 3.8 times. This effect was greatly reduced by prevention of direct cell contact by means of placement of a well insert, which also lessened the monocyte-induced proliferation in both serum-free and serum-containing medium. Furthermore, the transfer of the intracellular dye from RPE cells to cocultured monocytes indicates that RPE cells transferred parts of their cytoplasm to monocytes. • Conclusion: These observations underline the importance of protein leakage through a damaged blood-ocular barrier and of direct contact of monocytes/macrophages with RPE cells, as well as their reciprocal potentiating effect on RPE cell proliferation. Thus, early stabilization of the blood-ocular barrier, which would preclude or reduce protein leakage and invasion of inflammatory cells into the eye, could be a target for pharmacologic prevention of PVR.

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Authors and Affiliations

  1. University Eye Hospital, Mittlere Strasse 91, P.O. Box, CH-4012, Basel, Switzerland

    Roman Osusky

  2. Doheny Eye Institute and the Department of Ophthalmology, University of Southern California School of Medicine, 1450 San Pablo Street, 90033, Los Angeles, CA, USA

    Roman Osusky & Steven J. Ryan

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  1. Roman Osusky
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Osusky, R., Ryan, S.J. Retinal pigment epithelial cell proliferation: Potentiation by monocytes and serum. Graefe's Arch Clin Exp Ophthalmol 234 (Suppl 1), S76–S82 (1996). https://doi.org/10.1007/BF02343052

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  • DOI: https://doi.org/10.1007/BF02343052

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