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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.
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