Background: To examine the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and transforming growth factor beta 2 (TGF_β2) on bovine retinal pigment epithelial (RPE) cell migration and proliferation. Materials and Methods: Cultured bovine RPE cells were treated with 10 ng/ml PDGF, bFGF, aFGF, IGF-1, EGF, or TGF_β2. RPE cell migration studies were performed in multiwell plates confluently covered with RPE cells. After inhibition of proliferation and denudation of half of each well, cells were incubated with various growth factors. Migration was measured as the number of cells that had entered the denuded area after 20 h. RPE cell proliferation was determined by [³H]thymidine incorporation after growth factor stimulation for 24 h. Results: RPE cell migration was significantly enhanced after incubation with PDGF (stimulation of 213% compared to the negative control, p = 0.002), bFGF (206%, p = 0.003), aFGF (175%, p = 0.003), IGF-1 (150%, p = 0.003), and EGF (144%, p = 0.003). RPE cell proliferation was stimulated by bFGF (322% compared to the negative control, p < 0.005), PDGF (119%, p < 0.005), aFGF (121%, p < 0.005), and EGF (94%, p < 0.005). IGF-1 showed no significant effect on RPE cell proliferation; TGF_β2 displayed no effect on RPE cell migration nor on proliferation. Conclusions: The peptide growth factors PDGF, bFGF, aFGF, IGF-1, and EGF play an important role in initiating RPE cell migration. Basic FGF, PDGF, aFGF, and EGF stimulate RPE cell DNA synthesis.

Background: The retinal pigment epithelium (RPE) has been implicated in the development of diabetic retinopathy and it has been suggested that insulin-like growth factors (IGF) and glucose may be among those factors which are responsible for the RPE changes in diabetics. The purpose of this study was to investigate the effect of IGF-1, IGF-2, and glucose on the migration and proliferation of bovine RPE cells in vitro. Methods: Primary cultures of bovine RPE cells were established from freshly enucleated eyes and passages 5–8 were used for these experiments. RPE cell migration was studied in confluent RPE cultures grown in multiwell plates. After inhibition of proliferation with mitomycin C (10 µg/ml) and partial denudation of the RPE in each well, the cells were incubated with IGF-1 (10 ng/ml), IGF-2 (10 ng/ml) or glucose (10 mM). Migration was measured as the number of cells that had entered the denuded area after 20 h. RPE cell proliferation was determined by [³H]-thymidine incorporation after incubation with IGF-1, IGF-2, and glucose for 24 h. Statistical analysis was performed with the paired Student’s t test. Results: Exposure of RPE cells to IGF-1, IGF-2, and glucose resulted in a significantly higher RPE cell migration as compared to the control medium (p < 0.008) with 21, 20, 17, and 9 cells/raster field, respectively. Additionally, IGF-1 (p = 0.004) and IGF-2 (p = 0.008) but not glucose caused a statistically significant stimulation of DNA synthesis with 761, 747, and 593 ccpm, respectively, as compared to the negative control (352 ccpm). Conclusion: This study indicates that IGF-1 and IGF-2 influence RPE cell migration and proliferation. This is further evidence that these factors are among those which have to be kept in mind when trying to modulate the development of diabetic eye diseases.

Thalidomide and prednisolone were recently introduced as treatment modalities in age-related macular degeneration (AMD). Growth factor-induced activation of retinal pigment epithelial (RPE) cells is a crucial event in this disease. The purpose was to examine the effect of thalidomide and prednisolone on growth factor-preactivated RPE cells. Human RPE cells were stimulated with 10 ng/ml platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF) for 24 h. Afterwards, thalidomide (50 µg/ml) or prednisolone (100 ng/ml) were added for 24 h. RPE cell proliferation was determined by [³H]-thymidine incorporation. PDGF and bFGF significantly stimulated human RPE cell proliferation (p < 0.005), the value for VEGF stimulation was not significant (p = 0.3). The effect of the growth factors was diminished after addition of thalidomide and prednisolone (p < 0.005). The current study shows that the inhibitory properties of thalidomide and prednisolone remain even after growth factor activation of the cells.

Although the main effect of thalidomide, octreotide, and prednisolone when treating patients with choroidal neovascular membranes is probably related to the inhibition of angiogenesis it should be kept in mind that these substances may additionally inhibit RPE proliferation and migration.

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.