Growth Factor Combinations Modulate Human Retinal Pigment Epithelial Cell Proliferation

Purpose: Retinal pigment epithelial (RPE) cell proliferation is an important step in the pathogenesis of ocular diseases such as proliferative retinopathy. Growth factors play a major role in modulating the development and progression of these diseases. The aim of this study was to examine the effects of single growth factors as compared to growth factor combinations on the stimulation of RPE cell proliferation.

Methods: Human RPE cells were treated with 10 ng/ml IGF-1, PDGF, bFGF, EGF, VEGF, and TGFbeta(2), or with the combination of each of the growth factors. RPE cell proliferation was determined by [(3)H]-thymidine incorporation after growth factor stimulation for 24 hr.

Results: RPE cell proliferation was significantly increased when PDGF and bFGF were combined as compared to the single growth factor (p<0.005). There was a decrease in DNA synthesis for combined growth factors as compared to the single growth factor for IGF-1 plus TGFbeta(2) (p<0.05), IGF-1 plus VEGF (p<0.005), PDGF plus TGFbeta(2) (p<0.005), VEGF plus TGFbeta(2) (p<0.005 as compared to VEGF), and bFGF plus TGFbeta( 2) (p = 0.01 as compared to bFGF). The remaining growth factor combinations showed no significant synergistic effect on human RPE cell proliferation.

Conclusions: These data lead to the implication that DNA synthesis in human RPE cell culture is synergistically affected by certain growth factor combinations, but not by all of them. This observation may be important for a better understanding of growth factor interactions occuring in proliferative diseases in the eye.