FIGURE 7.

Potential RV-induced signaling pathways that trigger cellular responses. A, serum-starved hPRPE cells were treated with RV for 16 h, and then the cell lysates were subjected to Western blotting analysis using the antibodies indicated. Fold was calculated by first normalizing to the level of either Akt, MDM2, or β-Actin and then calculating the ratio of stimulated over basal (i.e. unstimulated) cells. This is representative of three independent experiments. B, pathway 1 indicates that vitreous stimulation leads to the activation of Erk, which phosphorylates Sp1, enhancing its association with the GC-rich motif in the MDM2 promoter. Pathway 2 indicates that vitreous stimulation leads to the activation of Akt and phosphorylation of MDM2, leading, in turn, to an increased association between MDM2 and p53. Both pathways resulted in degradation of p53, thereby enhancing cell proliferation and survival.