Involvement of calcium in retinal pigment epithelial cell proliferationand pigmentation.

PURPOSE. The aim of this study is to explore therole of intra-cellular calcium in the mechanism of co-regulation of retinalpigment epithelial cells (RPE) by vitreous fluid and platelet mitogens, inorder to evaluate the use of calcium modulating drugs in preventing RPE cellproliferation and contraction of fibrocellular membranes. METHODS. Monolayers of human RPE cells were loaded with Fura-2-AM and examinedin a fluorimeter for changes in intra-cellular free calcium in response toplatelet mitogens (PDG-FAB or TGFβ1) and vitreous fluid (containing vitreoussubstrate proteins), both alone or in combination. The effect of the calciumantagonists TMB8 and verapamil and the calmodulin antagonists J8 and tamoxifenwere then examined on RPE cell proliferation and pigmentation, both in thepresence and absence of vitreous substrate and platelet mitogens. RESULTS. We report that co-exposure of RPE cells to platelet mitogens andvitreous fluid produces an increase in intracellular free calcium of greaterduration than that with either PDG-FAB, TGFβ1 or vitreous fluid alone.Calcium and calmodulin antagonists significantly reduce RPE cell proliferationin both the presence and absence of vitreous substrate and platelet mitogens.Calcium antagonists also stimulate the accumulation of autofluorescent granuleswithin RPE cells. CONCLUSIONS. Calcium signalling plays a role in the co-regulation of RPEcells by vitreous substrate and platelet mitogens. Drugs that lower intracellularcalcium or inhibit calmodulin may offer an additional approach to preventingthe hyperproliferation of RPE cells in PVR. [ABSTRACT FROM AUTHOR]