INVOLVEMENT OF CALCIUM IN RETINAL-PIGMENT EPITHELIAL-CELL PROLIFERATION AND PIGMENTATION

Purpose. The aim of this study is to explore the role of intracellular calcium in the mechanism of co-regulation of retinal pigment epitheli al cells (RPE) by vitreous fluid and platelet mitogens, in order to ev aluate the use of calcium modulating drugs in preventing RPE cell prol iferation and contraction of fibrocellular membranes. Methods. Monolay ers of human RPE cells were loaded with Fura-2-AM and examined in a fl uorimeter for changes in intracellular free calcium in response to pla telet mitogens (PDG-FAB or TGF beta 1) and vitreous fluid (containing vitreous substrate proteins), both alone ol in combination. The effect of the calcium antagonists TMB8 and verapamil and the calmodulin anta gonists J8 and tamoxifen were then examined on RPE cell proliferation and pigmentation, both in the presence and absence of vitreous substra te and platelet mitogens. Results. We report that co-exposure of RPE c ells to platelet mitogens and vitreous fluid produces an increase in i ntracellular free calcium of greater duration than that with either PD G-FAB, TGF beta 1 or vitreous fluid alone. Calcium and calmodulin anta gonists significantly reduce RPE cell proliferation in both the presen ce and absence of vitreous substrate and platelet mitogens. Calcium an tagonists also stimulate the accumulation of autofluorescent granules within RPE cells. Conclusions. Calcium signalling plays a role in the co-regulation of RPE cells by vitreous substrate and platelet mitogens . Drugs that lower intracellular calcium or inhibit calmodulin may off er an additional approach to preventing the hyperproliferation of RPE cells in PVR.