Hs. Yu et al., MELATONIN INHIBITS THE PROLIFERATION OF RETINAL-PIGMENT EPITHELIAL (RPE) CELLS-INVITRO, In vitro cellular & developmental biology. Animal, 29A(5), 1993, pp. 415-418
The possible antiproliferative effect of melatonin on retinal pigment
epithelial (RPE) cells in vitro was investigated. Bovine RPE cells cul
tured in Ham's F12 medium supplemented with 10% fetal bovine serum had
a nuclear density of 73.6 +/- 6.1 nuclei/mm2 at 72 h after seeding. T
he nuclear density at this time-point was doubled if either 50 or 100
ng/ml human epidermal growth factors (hEGF) was added to the culture m
edium. When these hEGF-stimulated cells were treated with melatonin fr
om 10 to 500 pg/ml, the proliferation was suppressed with a dose-respo
nse relationship. At 250 and 500 pg/ml melatonin, the nuclear densitie
s of the melatonin-treated cells were similar to those of the control
cells. Using mitotically active SV-40 transformed human fetal RPE cell
s cultured in a serum-free medium, melatonin was also shown to be anti
proliferative. In the presence of 500 pg/ml melatonin, the proliferati
on of these cells was inhibited to 77% as compared to the control. The
se results were further supported by the reduced [H-3]thymidine uptake
in the melatonin-treated cells. We propose that melatonin, at physiol
ogic concentrations, has an antiproliferative effect, and that culture
d RPE cells stimulated to proliferate by either hEGF treatment or SV-4
0 transfection are responsive to melatonin. Melatonin may either inhib
it mitosis in actively dividing cells or modulate hEGF action.