Research Description

Major Results

We have shown that indirect suppression of serum insulin-like growth factor-I (IGF-I) through growth hormone (GH) suppression inhibits retinal NV. These results predict that direct inhibition of IGF-I will suppress NV and that blocking IGF-I receptor (IGF-IR) to prevent local as well as serum IGF-I effects would be more potent than inhibiting GH. Moreover, partial inhibition of both VEGF and serum IGF-I in combination might be more effective (and safer) than complete inhibition of either one alone.

With the use of an IGF-I agonist and IGF-I antagonist in a mouse model of ROP we will evaluate the therapeutic potential of IGF-I manipulation in the vaso-proliferative and vaso-obliterative phases of ROP. We will conduct parallel studies in vitro to evaluate the effect of IGF-I manipulation on endothelial cell proliferation and survival. We will determine which retinal cells normally express IGF-I, IGF-IR and IGF-I binding protein (IGF-IBP) mRNA and evaluate changes with blocking IGF-IR or decreasing serum IGF-I to evaluate toxicity of treatment. We will evaluate oxygen regulation of IGF-I, IGF-IR and IGF-I BP in vivo and in retinal endothelial cells in vitro. We will also evaluate the potential of combined control of VEGF and IGF-I in ROP and conduct parallel studies in vitro to determine the interaction between VEGF and IGF-I control of endothelial cell growth and survival.